bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D and rheumatoid arthritis
Authors: Kostoglou-Athanassiou Ifigenia , Athanassiou Panagiotis , Lyraki Aikaterini , Raftakis Ioannis , Antoniadis Christodoulos
Published: December 2012

Objectives:

Vitamin D deficiency has been implicated in the pathogenesis of autoimmune diseases, such as diabetes mellitus type 1 and multiple sclerosis. Reduced vitamin D intake has been linked to increased susceptibility to the development of rheumatoid arthritis (RA) and vitamin D deficiency has been found to be associated with disease activity in patients with RA. The objective was to evaluate vitamin D status in patients with RA and to assess the relationship between vitamin D levels and disease activity.

Methods:

In a cohort of 44 patients with RA, 25-hydroxyvitamin D3 [25(OH)D3] levels, parathyroid hormone levels, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured. Disease activity was evaluated by calculating the 28-joint Disease Activity Score (DAS28). A control group ( n = 44), matched for age and sex, was evaluated as well.

Results:

In the cohort of 44 patients with RA 25(OH)D3 levels were found to be low compared with the control group, 25(OH)D3 being 15.26 ± 1.07 ng/ml [mean ± standard error of the mean (SEM)] and 25.8 ± 1.6 ng/ml in the patient and control group respectively (Student’s t test, p < 0.001). Parathyroid hormone levels were 71.08 ± 7.02 pg/ml (mean ± SEM) (normal values 10.0–65.0 pg/ml), CRP 7.6 ± 1.57 mg/litre (mean ± SEM) (normal values < 3 mg/litre) and ESR was 38.0 ± 4.6 mm/h (mean ± SEM) in the group of patients with RA. Levels of 25(OH)D3 were found to be negatively correlated to the DAS28, the correlation coefficient being −0.084. Levels of 25(OH)D3 were also found to be negatively correlated to CRP and ESR, the correlation coefficient being –0.115 and −0.18, respectively.

Conclusion:

It appears that vitamin D deficiency is highly prevalent in patients with RA, and that vitamin D deficiency may be linked to disease severity in RA. As vitamin D deficiency has been linked to diffuse musculoskeletal pain, these results have therapeutic implications. Vitamin D supplementation may be needed both for the prevention of osteoporosis as well as for pain relief in patients with RA.
The deletion of bacterial dynamin and flotillin genes results in pleiotrophic effects on cell division, cell growth and in cell shape maintenance
Authors: Dempwolff Felix , Wischhusen Hanna M , Specht Mara , Graumann Peter L
Published: December 2012

Background

In eukaryotic cells, dynamin and flotillin are involved in processes such as endocytosis and lipid raft formation, respectively. Dynamin is a GTPase that exerts motor-like activity during the pinching off of vesicles, while flotillins are coiled coil rich membrane proteins with no known enzymatic activity. Bacteria also possess orthologs of both classes of proteins, but their function has been unclear.

Results

We show that deletion of the single dynA or floT genes lead to no phenotype or a mild defect in septum formation in the case of the dynA gene, while dynA floT double mutant cells were highly elongated and irregularly shaped, although the MreB cytoskeleton appeared to be normal. DynA colocalizes with FtsZ, and the dynA deletion strain shows aberrant FtsZ rings in a subpopulation of cells. The mild division defect of the dynA deletion is exacerbated by an additional deletion in ezrA, which affects FtsZ ring formation, and also by the deletion of a late division gene (divIB), indicating that DynA affects several steps in cell division. DynA and mreB deletions generated a synthetic defect in cell shape maintenance, showing that MreB and DynA play non-epistatic functions in cell shape maintenance. TIRF microscopy revealed that FloT forms many dynamic membrane assemblies that frequently colocalize with the division septum. The deletion of dynA did not change the pattern of localization of FloT, and vice versa, showing that the two proteins play non redundant roles in a variety of cellular processes. Expression of dynamin or flotillin T in eukaryotic S2 cells revealed that both proteins assemble at the cell membrane. While FloT formed patch structures, DynA built up tubulated structures extending away from the cells.

Conclusions

Bacillus subtilis dynamin ortholog DynA plays a role during cell division and in cell shape maintenance. It shows a genetic link with flotillin T, with both proteins playing non-redundant functions at the cell membrane, where they assemble even in the absence of any bacterial cofactor.
In vitro and in vivo characterization of DNA delivery using recombinant Lactococcus lactis expressing a mutated form of L. monocytogenes Internalin A
Authors: de Azevedo Marcela , Karczewski Jurgen , Lefévre François , Azevedo Vasco , Miyoshi Anderson , Wells Jerry M , Langella Philippe , Chatel Jean-Marc
Published: December 2012

Background

The use of food-grade Lactic Acid Bacteria (LAB) as DNA delivery vehicles represents an attractive strategy to deliver DNA vaccines at the mucosal surfaces as they are generally regarded as safe (GRAS). We previously showed that either native Lactococcus lactis (LL) or recombinant invasive LL expressing Fibronectin Binding Protein A of Staphylococcus aureus (LL-FnBPA+) or Internalin A of Listeria monocytogenes (LL-InlA+), were able to deliver and trigger DNA expression by epithelial cells, either in vitro or in vivo. InlA does not bind to its receptor, the murine E-cadherin, thus limiting the use of LL-InlA+ in in vivo murine models. Moreover, FnBPA binds to its receptors, integrins, via fibronectin introducing another limiting factor. In order to avoid the limitations of LL-InlA+ and LL-FnBPA+, a new L. lactis strain was engineered to produce a previously described mutated form of InlA (LL-mInlA+) allowing the binding of mInlA on murine E-cadherin.

Results

After showing the expression of mInLA at the surface of LL-mInlA+ strain, in vitro gentamycin survival assay in Caco-2 cells showed that LL-mInlA+ is 1000 times more invasive than LL. LL-mInlA+ invasivity was also validated by fluorescence microscopy. LL and LL-mInlA+ were transformed with pValacBLG, a plasmid containing the cDNA of bovine β-Lactoglobulin (BLG), resulting in strains LL-BLG and LL-mInlA+BLG. The plasmid transfer in vitro using LL-mInlA+BLG was increased 10 times compared to LL-BLG. Moreover, the number of mice producing BLG in isolated enterocytes after oral administration of LL-mInlA+BLG in vivo was slightly higher than after oral administration of LL-BLG.

Conclusions

We confirmed in this study that the production of mInlA at the surface of L. lactis is a promising strategy for plasmid transfer in vitro and in vivo.
Determinants of acceptance of cervical cancer screening in Dar es Salaam, Tanzania
Authors: Kahesa Crispin , Kjaer Susanne , Mwaiselage Julius , Ngoma Twalib , Tersbol Britt , Dartell Myassa , Rasch Vibeke
Published: December 2012

Objective

To describe how demographic characteristics and knowledge of cervical cancer influence screening acceptance among women living in Dar es Salaam, Tanzania.

Methods

Multistage cluster sampling was carried out in 45 randomly selected streets in Dar es Salaam. Women between the ages of 25–59 who lived in the sampled streets were invited to a cervical cancer screening; 804 women accepted and 313 rejected the invitation. Information on demographic characteristics and knowledge of cervical cancer were obtained through structured questionnaire interviews.

Results

Women aged 35–44 and women aged 45–59 had increased ORs of 3.52 and 7.09, respectively, for accepting screening. Increased accepting rates were also found among single women (OR 2.43) and among women who had attended primary or secondary school (ORs of 1.81 and 1.94). Women who had 0–2 children were also more prone to accept screening in comparison with women who had five or more children (OR 3.21). Finally, knowledge of cervical cancer and awareness of the existing screening program were also associated with increased acceptance rates (ORs of 5.90 and 4.20).

Conclusion

There are identifiable subgroups where cervical cancer screening can be increased in Dar es Salaam. Special attention should be paid to women of low education and women of high parity. In addition, knowledge and awareness raising campaigns that goes hand in hand with culturally acceptable screening services will likely lead to an increased uptake of cervical cancer screening.
Multidisciplinary approach to management of maternal asthma (MAMMA [copyright]): the PROTOCOL for a randomized controlled trial
Authors: Lim Angelina , Stewart Kay , Abramson Michael J , Walker Susan P , George Johnson
Published: December 2012

Background

Uncontrolled asthma during pregnancy is associated with the maternal hazards of disease exacerbation, and perinatal hazards including intrauterine growth restriction and preterm birth. Interventions directed at achieving better asthma control during pregnancy should be considered a high priority in order to optimise both maternal and perinatal outcomes. Poor compliance with prescribed asthma medications during pregnancy and suboptimal prescribing patterns to pregnant women have both been shown to be contributing factors that jeopardise asthma control. The aim is to design and evaluate an intervention involving multidisciplinary care for women experiencing asthma in pregnancy.

Methods/design

A pilot single-blinded parallel-group randomized controlled trial testing a Multidisciplinary Approach to Management of Maternal Asthma (MAMMA©) which involves education and regular monitoring. Pregnant women with asthma will be recruited from antenatal clinics in Victoria, Australia. Recruited participants, stratified by disease severity, will be allocated to the intervention or the usual care group in a 1:1 ratio. Both groups will be followed prospectively throughout pregnancy and outcomes will be compared between groups at three and six months after recruitment to evaluate the effectiveness of this intervention. Outcome measures include Asthma Control Questionnaire (ACQ) scores, oral corticosteroid use, asthma exacerbations and asthma related hospital admissions, and days off work, preventer to reliever ratio, along with pregnancy and neonatal adverse events at delivery. The use of FEV1/FEV6 will be also investigated during this trial as a marker for asthma control.

Discussion

If successful, this model of care could be widely implemented in clinical practice and justify more funding for support services and resources for these women. This intervention will also promote awareness of the risks of poorly controlled asthma and the need for a collaborative, multidisciplinary approach to asthma management during pregnancy. This is also the first study to investigate the use of FEV1/FEV6 as a marker for asthma control during pregnancy.

Trial registration

Australian New Zealand Clinical Trials Registry (ACTRN12612000681853)
Expression of recombinant staphylokinase in the methylotrophic yeast Hansenula polymorpha
Authors: Moussa Manal , Ibrahim Mahmoud , El Ghazaly Maria , Rohde Jan , Gnoth Stefan , Anton Andreas , Kensy Frank , Mueller Frank
Published: December 2012

Background

Currently, the two most commonly used fibrinolytic agents in thrombolytic therapy are recombinant tissue plasminogen activator (rt-PA) and streptokinase (SK). Whereas SK has the advantage of substantially lower costs when compared to other agents, it is less effective than either rt-PA or related variants, has significant allergenic potential, lacks fibrin selectivity and causes transient hypotensive effects in high dosing schedules. Therefore, development of an alternative fibrinolytic agent having superior efficacy to SK, approaching that of rt-PA, together with a similar or enhanced safety profile and advantageous cost-benefit ratio, would be of substantial importance. Pre-clinical data suggest that the novel fibrinolytic recombinant staphylokinase (rSAK), or related rSAK variants, could be candidates for such development. However, since an efficient expression system for rSAK is still lacking, it has not yet been fully developed or evaluated for clinical purposes. This study’s goal was development of an efficient fermentation process for the production of a modified, non-glycosylated, biologically active rSAK, namely rSAK-2, using the well-established single cell yeast Hansenula polymorpha expression system.

Results

The development of an efficient large scale (80 L) Hansenula polymorpha fermentation process of short duration for rSAK-2 production is described. It evolved from an initial 1mL HTP methodology by successive scale-up over almost 5 orders of magnitude and improvement steps, including the optimization of critical process parameters (e.g. temperature, pH, feeding strategy, medium composition, etc.). Potential glycosylation of rSAK-2 was successfully suppressed through amino acid substitution within its only N-acetyl glycosylation motif. Expression at high yields (≥ 1g rSAK-2/L cell culture broth) of biologically active rSAK-2 of expected molecular weight was achieved.

Conclusion

The optimized production process described for rSAK-2 in Hansenula polymorpha provides an excellent, economically superior, manufacturing platform for a promising therapeutic fibrinolytic agent.
VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity
Authors: Malykhina Anna P , Lei Qi , Erickson Chris S , Epstein Miles L , Saban Marcia R , Davis Carole A , Saban Ricardo
Published: December 2012

Background

This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity.

In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor.

To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments.

Results

In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation.

Conclusions

For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and enhanced VEGF content may be associated with visceral hyperalgesia, abdominal discomfort, and/or pelvic pain.
The biochemistry of acetaminophen hepatotoxicity and rescue: a mathematical model
Authors: Ben-Shachar Rotem , Chen Yifei , Luo Shishi , Hartman Catherine , Reed Michael , Nijhout H Frederik
Published: December 2012

Background

Acetaminophen (N-acetyl-para-aminophenol) is the most widely used over-the-counter or prescription painkiller in the world. Acetaminophen is metabolized in the liver where a toxic byproduct is produced that can be removed by conjugation with glutathione. Acetaminophen overdoses, either accidental or intentional, are the leading cause of acute liver failure in the United States, accounting for 56,000 emergency room visits per year. The standard treatment for overdose is N-acetyl-cysteine (NAC), which is given to stimulate the production of glutathione.

Methods

We have created a mathematical model for acetaminophen transport and metabolism including the following compartments: gut, plasma, liver, tissue, urine. In the liver compartment the metabolism of acetaminophen includes sulfation, glucoronidation, conjugation with glutathione, production of the toxic metabolite, and liver damage, taking biochemical parameters from the literature whenever possible. This model is then connected to a previously constructed model of glutathione metabolism.

Results

We show that our model accurately reproduces published clinical and experimental data on the dose-dependent time course of acetaminophen in the plasma, the accumulation of acetaminophen and its metabolites in the urine, and the depletion of glutathione caused by conjugation with the toxic product. We use the model to study the extent of liver damage caused by overdoses or by chronic use of therapeutic doses, and the effects of polymorphisms in glucoronidation enzymes. We use the model to study the depletion of glutathione and the effect of the size and timing of N-acetyl-cysteine doses given as an antidote. Our model accurately predicts patient death or recovery depending on size of APAP overdose and time of treatment.

Conclusions

The mathematical model provides a new tool for studying the effects of various doses of acetaminophen on the liver metabolism of acetaminophen and glutathione. It can be used to study how the metabolism of acetaminophen depends on the expression level of liver enzymes. Finally, it can be used to predict patient metabolic and physiological responses to APAP doses and different NAC dosing strategies.
Prognostic significance of thyroid or cricoid cartilage invasion in laryngeal or hypopharyngeal cancer treated with organ preserving strategies
Authors: Wagner Marcus M , Curé Joel K , Caudell Jimmy J , Spencer Sharon A , Nabell Lisle M , Carroll William R , Bonner James A
Published: December 2012

Background

The utility of definitive radiotherapy (RT) for locoregionally advanced squamous cell carcinoma (SCC) of the larynx or hypopharynx in the setting of thyroid or cricoid cartilage invasion (TCCI) is controversial. A retrospective review of our experience was performed.

Methods

Our institutional database of patients with SCC of the head and neck treated with radiotherapy (90% received concurrent systemic therapy) between 1995 and 2009 was queried. We identified 87 patients with T3-4 laryngeal or T4 hypopharyngeal cancer for whom initial head and neck imaging was available for review. Imaging of all patients was reviewed by a single radiologist specializing in neuroradiology. The presence and extent of TCCI was determined and used for stratification.

Results

Median follow-up was 34 months. TCCI was found in 25 (29%) patients, eight limited to the inner cortex and another 17 involving both cortices. Local control (LC) was not significantly affected by TCCI limited to the inner cortex. However, TCCI involving both cortices was correlated with diminished LC at 2 years compared to the group of patients with no or minor invasion (55% vs. 81%, p=0.045). However, TCCI involving both cortices was not associated with significantly reduced rates of survival with a functional larynx, or overall survival (OS).

Conclusions

Our results suggest that the rate of LC of T3-4 laryngeal or T4 hypopharyngeal SCC treated with definitive RT is not affected by TCCI of the inner cortex. Although decreased LC was significantly associated with TCCI involving both cortices, this factor did not appear to result in reduced rates of survival with a functional larynx or OS. Therefore, organ preservation may remain an option in these patients.
Umbilical cord blood-derived mesenchymal stem cells consist of a unique population of progenitors co-expressing mesenchymal stem cell and neuronal markers capable of instantaneous neuronal differentiation
Authors: Divya Mundackal S , Roshin George E , Divya Thulasi S , Rasheed Vazhanthodi Abdul , Santhoshkumar Thankayyan R , Elizabeth Kandathil E , James Jackson , Pillai Radhakrishna M
Published: December 2012

Introduction

Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) are self-renewing multipotent progenitors with the potential to differentiate into multiple lineages of mesoderm, in addition to generating ectodermal and endodermal lineages by crossing the germline barrier. In the present study we have investigated the ability of UCB-MSCs to generate neurons, since we were able to observe varying degrees of neuronal differentiation from a few batches of UCB-MSCs with very simple neuronal induction protocols whereas other batches required extensive exposure to combination of growth factors in a stepwise protocol. Our hypothesis was therefore that the human UCB-MSCs would contain multiple types of progenitors with varying neurogenic potential and that the ratio of the progenitors with high and low neurogenic potentials varies in different batches of UCB.

Methods

In total we collected 45 UCB samples, nine of which generated MSCs that were further expanded and characterized using immunofluorescence, fluorescence-activated cell sorting and RT-PCR analysis. The neuronal differentiation potential of the UCB-MSCs was analyzed with exposure to combination of growth factors.

Results

We could identify two different populations of progenitors within the UCB-MSCs. One population represented progenitors with innate neurogenic potential that initially express pluripotent stem cell markers such as Oct4, Nanog, Sox2, ABCG2 and neuro-ectodermal marker nestin and are capable of expanding and differentiating into neurons with exposure to simple neuronal induction conditions. The remaining population of cells, typically expressing MSC markers, requires extensive exposure to a combination of growth factors to transdifferentiate into neurons. Interesting to note was that both of these cell populations were positive for CD29 and CD105, indicating their MSC lineage, but showed prominent difference in their neurogenic potential.

Conclusion

Our results suggest that the expanded UCB-derived MSCs harbor a small unique population of cells that express pluripotent stem cell markers along with MSC markers and possess an inherent neurogenic potential. These pluripotent progenitors later generate cells expressing neural progenitor markers and are responsible for the instantaneous neuronal differentiation; the ratio of these pluripotent marker expressing cells in a batch determines the innate neurogenic potential.
A fast reduced-rank interpolation method for prestack seismic volumes that depend on four spatial dimensions
Authors: Gao Jianjun , Sacchi Mauricio D. , Chen Xiaohong
Published: December 2012

Rank reduction strategies can be employed to attenuate noise and for prestack seismic data regularization. We present a fast version of Cadzow reduced-rank reconstruction method. Cadzow reconstruction is implemented by embedding 4D spatial data into a level-four block Toeplitz matrix. Rank reduction of this matrix via the Lanczos bidiagonalization algorithm is used to recover missing observations and to attenuate random noise. The computational cost of the Lanczos bidiagonalization is dominated by the cost of multiplying a level-four block Toeplitz matrix by a vector. This is efficiently implemented via the 4D fast Fourier transform. The proposed algorithm significantly decreases the computational cost of rank-reduction methods for multidimensional seismic data denoising and reconstruction. Synthetic and field prestack data examples are used to examine the effectiveness of the proposed method.
Environmental interaction influences muscle activation strategy during sand-swimming in the sandfish lizard Scincus scincus
Authors: Sharpe Sarah S. , Ding Yang , Goldman Daniel I.
Published: December 2012

Animals like the sandfish lizard (Scincus scincus) that live in desert sand locomote on and within a granular medium whose resistance to intrusion is dominated by frictional forces. Recent kinematic studies revealed that the sandfish utilizes a wave of body undulation during swimming. Models predict that a particular combination of wave amplitude and wavelength yields maximum speed for a given frequency, and experiments have suggested that the sandfish targets this kinematic waveform. To investigate the neuromechanical strategy of the sandfish during walking, burial and swimming, here we use high-speed X-ray and visible light imaging with synchronized electromyogram (EMG) recordings of epaxial muscle activity. While moving on the surface, body undulation was not observed and EMG showed no muscle activation. During subsurface sand-swimming, EMG revealed an anterior-to-posterior traveling wave of muscle activation which traveled faster than the kinematic wave. Muscle activation intensity increased as the animal swam deeper into the material but was insensitive to undulation frequency. These findings were in accord with empirical force measurements, which showed that resistance force increased with depth but was independent of speed. The change in EMG intensity with depth indicates that the sandfish targets a kinematic waveform (a template) that models predict maximizes swimming speed and minimizes the mechanical cost of transport as the animal descends into granular media. The differences in the EMG pattern compared with EMG of undulatory swimmers in fluids can be attributed to the friction-dominated intrusion forces of granular media.
Real-time measurement of metabolic rate during freezing and thawing of the wood frog,Rana sylvatica: implications for overwinter energy use
Authors: Sinclair Brent J. , Stinziano Joseph R. , Williams Caroline M. , MacMillan Heath A. , Marshall Katie E. , Storey Kenneth B.
Published: December 2012

Ectotherms overwintering in temperate ecosystems must survive low temperatures while conserving energy to fuel post-winter reproduction. Freeze-tolerant wood frogs, Rana sylvatica, have an active response to the initiation of ice formation that includes mobilising glucose from glycogen and circulating it around the body to act as a cryoprotectant. We used flow-through respirometry to measure CO2 production () in real time during cooling, freezing and thawing. CO2 production increases sharply at three points during freeze–thaw: at +1°C during cooling prior to ice formation (total of 104±17 μl CO2 frog−1 event−1), at the initiation of freezing (565±85 μl CO2 frog−1 freezing event−1) and after the frog has thawed (564±75 μ l CO2 frog−1 freezing event−1). We interpret these increases in metabolic rate to represent the energetic costs of preparation for freezing, the response to freezing and the re-establishment of homeostasis and repair of damage after thawing, respectively. We assumed that frogs metabolise lipid when unfrozen and that carbohydrate fuels metabolism during cooling, freezing and thawing, and when frozen. We then used microclimate temperature data to predict overwinter energetics of wood frogs. Based on the freezing and melting points we measured, frogs in the field were predicted to experience as many as 23 freeze–thaw cycles in the winter of our microclimate recordings. Overwinter carbohydrate consumption appears to be driven by the frequency of freeze–thaw events, and changes in overwinter climate that affect the frequency of freeze–thaw will influence carbohydrate consumption, but changes that affect mean temperatures and the frequency of winter warm spells will modify lipid consumption.
Value judgements and conceptual tensions: decision-making in relation to hospital discharge for people with dementia
Authors: Greener Helen , Poole Marie , Emmett Charlotte , Bond John , Louw Stephen J , Hughes Julian C
Published: December 2012

We reflect, using a vignette, on conceptual tensions and the value judgements that lie behind difficult decisions about whether or not the older person with dementia should return home or move into long-term care following hospital admission. The paper seeks, first, to expose some of the difficulties arising from the assessment of residence capacity, particularly around the nature of evaluative judgements and conceptual tensions inherent in the legal approach to capacity. Secondly, we consider the assessment of best interests around place of residence, which demonstrates significant conceptual tensions. In addition, ‘best interests’ raise issues around the perception of risk and the perceptions of the family and crucially involve the notions of autonomy and trust. Finally, we not only gesture at some practical considerations based on insights from values-based medicine, but also make the suggestion that we require tighter functional assessments of residence capacity coupled with broader judgements about best interests.
IEEN workshop report: aims and methods in interdisciplinary and empirical bioethics
Authors: Owens John , Ives Jonathan , Cribb Alan
Published: December 2012

Bioethics is a diverse field that accommodates a broad range of perspectives and disciplines. The recent explosion of literature on methods in interdisciplinary and empirical ethics might appear, however, to overshadow the fact that ‘bioethics’ has long been an interdisciplinary field. The Interdisciplinary and Empirical Ethics Network (IEEN) was established, with funding from the Wellcome Trust, to facilitate critical and constructive discussion around the nature of this disciplinary diversity and shift focus away from the ‘empirical turn’, towards the ongoing development of bioethics as an evolving field of interdisciplinary study. In April 2012 the IEEN organized a workshop at the Centre for Public Policy Research, King's College London, dedicated to discussing the relationship between aims and methods in interdisciplinary and empirical bioethics. This paper reports on that first meeting.
Delaying embryo development by storing at 4°C for synchronization to recipients in microinjection technique in rabbits
Authors: Nishijima K , Liu E , Yamaguchi S , Tanaka M , Morimoto M , Watanabe T , Fan J , Kitajima S
Published: December 2012

Short-term storage of embryos at low temperature induces developmental arrest of the embryo and would appear to be a valuable aid in embryo-transfer techniques to avoid wasting embryos. Embryo storage at 4°C was examined to allow synchronization with embryo-transfer recipients using the microinjection technique. Superovulation was induced in female Japanese White donor rabbits four days before mating with males. At the same time, control recipients were injected with human chorionic gonadotropin (hCG) to allow synchronization (R1); the hCG injections were delayed by 24 h in the experimental group (R2). DNA constructs for expressing human C-reactive protein or apolipoprotein AII were microinjected into the male pronuclei of the ova. The microinjected embryos were immediately transferred to recipients (R1) or stored at 4°C in phosphate-buffered saline containing 10% fetal bovine serum. After 17–20 h, the stored embryos were incubated at 37°C for one hour, and the morphologically normal embryos were transferred to recipients (R2). In the R1 rabbits, 855 embryos were transferred to 29 recipients, and 72.4% of the recipients became pregnant. Seven of the 84 offspring were transgenic. In the R2 rabbits, 478 embryos were transferred to 16 recipients, and 62.5% of the recipients became pregnant. Two of the 39 offspring were transgenic. There were no differences in pregnancy rate, litter size and transgenic integration rate between R1 and R2. These results suggest that the short-term 4°C storage of microinjected embryos can be a valuable method for synchronization with recipients, and reducing wastage of embryos and the sacrifice of rabbits.
Targeting of TGFβ signature and its essential component CTGF by miR-18 correlates with improved survival in glioblastoma
Authors: Fox Jamie L. , Dews Michael , Minn Andy J. , Thomas-Tikhonenko Andrei
Published: December 2012

The miR-17∼92 cluster is thought to be an oncogene, yet its expression is low in glioblastoma multiforme (GBM) cell lines. This could allow unfettered expression of miR-17∼92 target genes such as connective tissue growth factor (CTGF; or CCN2), which is known to contribute to GBM pathogenesis. Indeed, microRNA-18a (but not other miR-17∼92 members) has a functional site in the CTGF 3′ UTR, and its forced reexpression sharply reduces CTGF protein and mRNA levels. Interestingly, it also reduces the levels of CTGF primary transcript. The unexpected effects of miR-18a on CTGF transcription are mediated in part by direct targeting of Smad3 and ensuing weakening of TGFβ signaling. Having defined the TGFβ signature in GBM cells, we demonstrate a significant anti-correlation between miR-18 and TGFβ signaling in primary GBM samples from The Cancer Genome Atlas. Most importantly, high levels of miR-18 combined with low levels of the TGFβ metagene correlate with prolonged patient survival. Thus, low expression of the miR-17∼92 cluster, and specifically miR-18a, could significantly contribute to GBM pathogenesis.
Effects of Chemotherapy and Psychosocial Distress on Perceived Cognitive Disturbances in Asian Breast Cancer Patients
Authors: Cheung Yin Ting , Shwe Maung , Chui Wai Keung , Chay Wen Yee , Ang Soo Fan , Dent Rebecca Alexandra , Yap Yoon Sim , Lo Soo Kien , Ng Raymond Chee Hui , Chan Alexandre
Published: December 2012

Background:

There is conflicting evidence on the effect of chemotherapy and psychosocial distress on perceived cognitive changes in cancer patients.

Objective:

To compare the severity of perceived cognitive disturbance in Asian breast cancer patients receiving chemotherapy and those not receiving chemotherapy, and identify clinical characteristics associated with perceived cognitive disturbances.

Methods:

A cross-sectional, observational study was conducted at the largest cancer center in Singapore. Breast cancer patients receiving chemotherapy and not receiving chemotherapy completed the Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30), and Beck Anxiety Inventory to assess their perceived cognitive functioning, health-related quality of life, and anxiety, respectively. Multiple regression was conducted to delineate the factors associated with perceived cognitive disturbances.

Results:

A total of 85 breast cancer patients receiving chemotherapy and 81 not receiving chemotherapy were recruited. Chemotherapy patients experienced more fatigue (QLQ-C30 fatigue scores: 33.3 vs 22.2 points; p = 0.005) and moderate-to-severe anxiety (21.9% vs 8.6%; p = 0.002) compared to non-chemotherapy patients. Non-chemotherapy patients reported better perceived cognitive functioning than those who received chemotherapy (FACT-Cog scores: 124 vs 110 points, respectively; p < 0.001). Chemotherapy and endocrine therapy were strongly associated with perceived cognitive disturbances (p < 0.001 and 0.021, respectively). The interacting effect between anxiety and fatigue was moderately associated with perceived cognitive disturbances (β = -0.29; p = 0.037).

Conclusions:

Chemotherapy and endocrine treatment were associated with significant cognitive disturbances among Asian breast cancer patients. Psychosocial factors could be used to identify cancer patients who are more susceptible to cognitive disturbances in the clinical setting.
The Contribution of Chinese FDI to Africa's Pre Crisis Growth Surge
Authors: Whalley John , Weisbrod Aaron
Published: December 2012

In the 3 years before the 2008 Financial Crisis, GDP growth in Sub-Saharan Africa (averaged over individual economies) was around 6%, or 2 percentage points above mean growth rates for the preceding 10 years. This period also coincided with significant Chinese FDI flows into these countries, accounting for up to 10% of total inward FDI flows for certain countries in these years. We use growth accounting methods to assess what portion of this elevated growth can be attributed to Chinese inward FDI. We follow Solow (1957), Dennison (1962), and others and use data for individual economies between 1990 and 2008 to calculate Solow residuals for these years for individual economies. We use capital stock data, workforce, and factor share data by country. Capital stock data is unavailable directly and so we use perpetual inventory methods to construct the data. Factor shares come from UN National Accounts data. We then run counterfactual growth accounting experiments for thirteen Sub-Saharan African countries excluding Chinese FDI inflows for 2005-2007 and also 2003-2009. Our individual results vary by year and country, but there are several year/country combinations where Chinese FDI contributed to an additional one half of a percentage point or above to GDP growth. These results suggest that a significant, even if in some cases small, portion of the elevated growth in Sub-Saharan Africa in the three years before the Financial Crisis and also in the two years afterwards (2008-2009) can be attributed to Chinese inward investment.
The "Great Moderation" in a Dual Exchange Rate Regime
Authors: Arndt Sven W.
Published: December 2012

In the early nineties, the U.S. economy was emerging from a brief slump, monetary policy was easy, and economic activity recovered quickly during the decade, with GDP eventually reaching and then passing the consensus full employment level. Yet aggregate inflation remained surprisingly subdued. This moderation in prices at the aggregate level persuaded policy makers to allow the easy-money stance to continue in spite of the presence of inflation in non-tradables and in housing and construction in particular. This paper uses a flex-price, mixed-exchange rate model to examine some of the major contributing factors to economic developments in the two-decade period that ended in the financial meltdown and the great recession. It argues that Chinese exchange rate manipulation and China's preference for holding dollar reserves were important contributing factors. On the U.S. side, failure to understand the importance of differencial inflation patterns in tradables and non-tradables sectors, and especially failure to see inflation in housing and construction as goods rather than asset inflation, allowed monetary expansion to last much longer than it should have.
Globalization, Growth and Poverty
Authors: Salvatore Dominick , Campano Fred
Published: December 2012

The paper examines the change in the income distribution of developed and developing countries over the recent period of globalization from 1980 to the present. The change in the income distribution of developing countries is also measured for those developing countries that globalized and those that did not. The paper finds that in terms of the three major measures of central tendency, the real personal income ratios between developed and developing countries have been substantially reduced during the 1980-2005 period of rapid globalization, especially at the mode, where the most severe poverty lies.
Adsorption isotherms in landfill leachate treatment using powdered activated carbon augmented sequencing batch reactor technique: Statistical analysis by response surface methodology
Authors: Aziz Shuokr Qarani , Aziz Dr. Hamidi Abdul , Yusoff Mohd Suffian , Mojiri Amin , Amr Salem S. Abu
Published: December 2012

Landfill leachate was treated using non-powdered activated carbon sequencing batch reactor (NPAC-SBR) and powdered activated carbon (PAC) augmented SBR (PAC-SBR) processesto examine Langmuir and Freundlichadsorption isothermsin the SBR technique.Response surface methodology (RSM) was used for the experimental design and statistical analysis.Based on the obtained results, the maximum adsorption capacitiesof ammonia nitrogen (NH3-N), color, and chemical oxygen demand (COD) for the Langmuir adsorption isotherm were 5.63 mg/g, 25.30 Pt.Co/g, and 13.21 mg/g,respectively, whereas for the Freundlichadsorption isotherm, thesewere 6 mg/g, 46.29Pt.Co/g, and 15.41 mg/g, respectively.Generally, Freundlich isotherm values for NH3-N, color, and COD were higher than Langmuir isotherm values.The NH3-N adsorption on PAC was lower than the color and COD adsorptions because a great part of NH3-Nwas biologically removed in the SBR process.Increasing aeration rate and contact times in the SBR processes increased the adsorption isotherms of NH3-N, color, and COD on PAC
Researchers and Small-scale Entrepreneurship
Authors: Garcia-Padilla Antonio
Published: December 2012

For decades, the Commonwealth of Puerto Rico relied on tax incentives to promote itself as a manufacturing hub for pharmaceutical and medical devices. These tax policies, coupled with a well-trained work force, turned Puerto Rico into one of the most vibrant manufacturing centers in the world. More than 40 companies operating in Puerto Rico created over 26,000 direct jobs and contributed another 50,000 indirect employments. Many of the top-selling prescription drugs in the market are manufactured in Puerto Rico. Lipitor, Viagra, Zocor, Zoloft, and many of the well-known blockbuster drugs came from the Island. As it encountered the tensions of the 21st Century, Puerto Rico realized that manufacturing alone cannot secure future economic success. Competition from the world’s emerging economy in Asia and Latin America was becoming stronger every day. China and India are capable of producing drugs with the same level of proficiency and at lower costs. Further, the pipeline for big blockbuster drugs is rapidly drying down. To maintain its role in the global health market, Puerto Rico realized that it must use its trained people not only to manufacture, but to research, design, develop and test products. Through clinical trials for emerging medicines, complex cell analysis and clinical diagnostic projects, Puerto Rico planned to play a role in creating the next generation of scientific discoveries; that it must move into the value line of its industrial base from manufacturing to drug development and testing. From the 1970’s on, in positioning itself as manufacturing hub, Puerto Rico relied on the fiscal autonomy that its current political status grants to the Island, and aggressively exempted from income and other taxes the profits that the pharmaceutical and medical devices companies generate in Puerto Rico. As the Island seeks to emigrate from manufacturing to research and development, the tax issues are different. Simply said, income tax incentives are not relevant for research centers, since research centers are cost centers, not profit centers. Puerto Rico then turned to a new experiment in tax policy: tax exemptions for the personal income of highly competitive researchers living and working in the Island. Thus, Puerto Rico moved to attract and retain in Puerto Rico competitive researchers and to create incentives for non-competitive scientists already living in Puerto Rico to move into more competitive projects. This article will explain the process, and the tax measures adopted by the Commonwealth Puerto Rico towards that end, and explore the potential developments in such policies as they are implemented in the years ahead.
Mode 4 of WTO's General Agreement on Trade in Services: Can it spur Cross-Border Labor Mobility from Developing Countries?
Authors: Dowlah Caf
Published: December 2012

Liberalization of merchandize trade has brought forth extraordinary gains to world economy in recent decades. Available research, however, suggests that even greater benefits can result from the liberalization of global trade in services. Currently only about 20 percent of services are traded internationally although this sector accounts for more than half of global outputs, and exceeds 75 percent of GDP in high-income countries. Temporary movement of natural persons as service suppliers—as envisaged by GATS-Mode 4 of WTO—is one such services area which promises great benefits to both labor sending and receiving countries, but remains mired in a complex quagmire of trade and non-trade barriers as well as widespread misapprehensions. This paper argues that a basic convergence of economic interests seem to exist between the labor sending and receiving countries for liberalizing temporary movement of natural persons as service suppliers, and that, despite growing anti-immigration sentiments in developed countries, GATS-Mode 4 may be capable of spurring greater cross-border labor mobility.
Implications of a Weaker Form of Complementarity
Authors: Neill Jon R.
Published: December 2012

When a non-market good has existence value, the assumption of weak complementarity cannot be used to determine willingness to pay for that good. However, when this assumption is weakened, it is possible to place an upper bound on marginal willingness to pay even when the non-market good has existence value, and thereby, an upper bound on willingness to pay for changes in consumption of non-market goods can be established. Moreover, this upper bound may be relatively easy to compute.
Gain and Loss Domains and the Choice of Welfare Measure of Positive and Negative Changes
Authors: Knetsch Jack L. , Riyanto Yohanes E. , Zong Jichuan
Published: December 2012

Mounting evidence continues to suggest that people value changes in terms of a neutral reference state and that those in the domain of losses are commonly valued far more than those in the gains. Consequently, both negative and positive changes in the domain of losses, including mitigation of losses such as restoring environmental quality and reducing accident rates, may be more accurately valued with the minimum acceptable-compensation (WTA) measure, those in the domain of gains are more accurate with the maximum willingness-to-pay (WTP) measure. Current practice, that assumes equivalence and that all positive changes are considered as gains, is therefore likely to often seriously mislead.
Economic Costs and Benefits of Promoting Healthy Takeaway Meals at Workplace Canteens
Authors: Jensen Jørgen Dejgaard , Mørkbak Morten Raun , Nordström Jonas
Published: December 2012

Canteen Takeaway is a novel concept, which entails workplace canteens to utilise existing production capacity to supply packaged meals for employees to bring home. The concept has a potential to raise the average nutritional quality of employees’ diets. The purpose of the study is to assess the economic net gains for users, and for society as a whole, of promoting healthy canteen takeaway meals, using Danish workplaces as an example. The analytical framework for the study combines direct cost analyses, users’ willingness to pay estimated through a choice experiment and cost-of-illness methods to assess the net society costs and benefits associated with an extended use of canteen takeaway meals as a health promotion strategy. The results show that employees have a positive willingness to pay for health attributes in canteen takeaway meals, but with a minority having a highly negative willingness to pay for the canteen takeaway concept. The potential health effects of a healthy canteen takeaway programme are estimated to be positive, but modest in magnitude. The estimated costs of providing healthy canteen takeaway meals exceed the sum of average direct and indirect benefits. In conclusion, healthy CTA programmes seems to be an economically sustainable intervention at some workplaces, though the analysis does not fully support a full-scale implementation of healthy CTA programmes at Danish workplaces from a welfare economic perspective.