bluuebunny/crossref_metadata_2025 huggingface dataset:
The mechanics of flexor tendon adhesions
Authors: Branford O. A. , Lee D. A. , Bader D. L. , Grobbelaar A. O.
Published: December 2011

The mechanics of adhesions at a local tissue level have not been extensively studied. This study compared microstrains and macrostrains in adhesions of immobilized and mobilized partially lacerated flexor digitorum profundus tendons in a New Zealand White rabbit model. At 2 weeks, 50 digits were randomized to either gross tensile testing or micromechanical assessment, in which the movement of fluorescently labelled cell nuclei, acting as dynamic markers, was visualized using real-time confocal microscopy. The structural stiffness and load at failure of immobilized adhesions were 140% and 160% of that of mobilized adhesions, respectively, and both differences were statistically significant. Micromechanically, different patterns of loading and failure were observed. Mobilized adhesions exhibited over a three-fold higher local strain, which was less uniformly distributed. Confocal microscopy provided an accurate measure of local strain. For the first time, it has been possible to visualize, define, and quantify local adhesion tissue mechanics. Mobilization appears to favour the formation of sites expressing increased local strain responses or those predisposed to heterogeneity and localized failure.
Reconstruction of hypoplastic thumb using hemi-longitudinal metatarsal transfer
Authors: Chow C. S. , Ho P. C. , Tse W. L. , Hung L. K.
Published: December 2011

The treatment of hypoplastic thumb (modified Blauth’s type IIIb and IV) by pollicization is culturally unfavourable in the Chinese population and digit preservation is preferred. An innovative reconstruction method using a nonvascularized hemi-longitudinal metatarsal graft was performed in six cases with an average follow-up of 87.7 months. Overall hand function was good, as assessed using the Jebsen hand function test. Grip strength and pinch power were significantly weaker than the normal contralateral hand. There was no neurovascular or wound complication. The only donor site complication was a metatarsal fracture, which healed uneventfully with casting. There had been no permanent morbidity to the donor site, as all donor metatarsals hypertrophied and regained normal growth potentials. Linear growth of the transferred metatarsals was evident radiologically (average 1.5 mm/year). Free hemi-longitudinal metatarsal transfer is a feasible method with good functional outcome in the attainment of a 5-digit hand in patients with type IIIb/IV hypoplastic thumb.
Biomechanical considerations in the design of equipment to prevent sports injury
Authors: McIntosh Andrew S
Published: December 2011

The international market for sports equipment is enormous. One component of that market is explicitly equipment to prevent injury, and ideally all equipment should enable performance without causing injury. This paper will describe a biomechanical approach to the design of equipment to prevent sports injury. Elements in this approach include understanding and applying: injury risk management methods to set objectives; injury mechanisms; human tolerance to loads; range of sports loads (normal and abnormal); objectives of sport and sports skills; efficacy and effectiveness of current and past equipment; user expectations (usability, mass, aesthetics); standards requirements; setting performance objectives; identifying and testing materials; assessing materials and component testing; prototype testing; final product; and product evaluation and continuous control.
Aging and bone loss: new insights for the clinician
Authors: Demontiero Oddom , Vidal Christopher , Duque Gustavo
Published: December 2011

It is well known that the underlying mechanisms of osteoporosis in older adults are different than those associated with estrogen deprivation. Age-related bone loss involves a gradual and progressive decline, which is also seen in men. Markedly increased bone resorption leads to the initial fall in bone mineral density. With increasing age, there is also a significant reduction in bone formation. This is mostly due to a shift from osteoblastogenesis to predominant adipogenesis in the bone marrow, which also has a lipotoxic effect that affects matrix formation and mineralization. We review new evidence on the pathophysiology of age-related bone loss with emphasis upon the mechanism of action of current osteoporosis treatments. New potential treatments are also considered, including therapeutic approaches to osteoporosis in the elderly that focus on the pathophysiology and potential reversal of adipogenic shift in bone.
Disturbance of the OPG/RANK/RANKL pathway and systemic inflammation in COPD patients with emphysema and osteoporosis
Authors: Bai Peng , Sun Yongchang , Jin Jianmin , Hou Jia , Li Ran , Zhang Qing , Wang Yang
Published: December 2011

Background

Osteoporosis is one of the systemic features of COPD. A correlation between the emphysema phenotype of COPD and reduced bone mineral density (BMD) is suggested by some studies, however, the mechanisms underlying this relationship are unclear. Experimental studies indicate that IL-1β, IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema. The OPG/RANK/RANKL system is an important regulator of bone metabolism, and participates in the development of post-menopausal osteoporosis. Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied.

Methods

Eighty male patients (current or former smokers) completed a chest CT scan, pulmonary function test, dual x-ray absorptiometry measurements and questionnaires. Among these subjects, thirty patients with normal BMD and thirty patients with low BMD were selected randomly for measurement of IL-1β, IL-6, TNF-α (flow cytometry) and OPG/RANK/RANKL (ELISA). Twenty age-matched healthy volunteers were recruited as controls.

Results

Among these eighty patients, thirty-six had normal BMD and forty-four had low BMD. Age, BMI and CAT score showed significant differences between these two COPD groups (p < 0.05). The low-attenuation area (LAA%) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD (r = 0.741; p < 0.0001). Forward logistic regression analysis showed that only LAA% (p = 0.005) and BMI (p = 0.009) were selected as explanatory variables. The level of IL-1β was significantly higher in the COPD patients as compared to the normal controls (p < 0.05), but the difference between the two COPD groups did not reach significance. The levels of IL-6 and TNF-α among the three groups were significantly different (p < 0.05). The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls (p < 0.05), and correlated negatively with lumbar vertebral BMD, but positively with LAA%.

Conclusions

Radiographic emphysema is correlated with low BMD in current and former smokers with COPD. IL-1β, IL-6, TNF-α, and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD.
Biophysical and structural considerations for protein sequence evolution
Authors: Grahnen Johan A , Nandakumar Priyanka , Kubelka Jan , Liberles David A
Published: December 2011

Background

Protein sequence evolution is constrained by the biophysics of folding and function, causing interdependence between interacting sites in the sequence. However, current site-independent models of sequence evolutions do not take this into account. Recent attempts to integrate the influence of structure and biophysics into phylogenetic models via statistical/informational approaches have not resulted in expected improvements in model performance. This suggests that further innovations are needed for progress in this field.

Results

Here we develop a coarse-grained physics-based model of protein folding and binding function, and compare it to a popular informational model. We find that both models violate the assumption of the native sequence being close to a thermodynamic optimum, causing directional selection away from the native state. Sampling and simulation show that the physics-based model is more specific for fold-defining interactions that vary less among residue type. The informational model diffuses further in sequence space with fewer barriers and tends to provide less support for an invariant sites model, although amino acid substitutions are generally conservative. Both approaches produce sequences with natural features like dN/dS < 1 and gamma-distributed rates across sites.

Conclusions

Simple coarse-grained models of protein folding can describe some natural features of evolving proteins but are currently not accurate enough to use in evolutionary inference. This is partly due to improper packing of the hydrophobic core. We suggest possible improvements on the representation of structure, folding energy, and binding function, as regards both native and non-native conformations, and describe a large number of possible applications for such a model.
Blockade of leukocyte haptokinesis and haptotaxis by ketoprofen, diclofenac and SC-560
Authors: Paskauskas Saulius , Parseliunas Audrius , Kerkadze Vachtang , Nobiling Rainer , Schmidt Jan , Ryschich Eduard
Published: December 2011

Background

Nonsteroidal anti-inflammatory drugs (NSAID) represent a one of the most widely used anti-inflammatory substances. Their anti-inflammatory effects are mainly based on inhibition of cyclooxygenase. The potential direct effect of NSAID on leukocyte migration was poorly investigated. Using time-lapse microscopy and 96-well fluorescence-based assay, we studied the effect of three different NSAID, ketoprofen, diclofenac and SC-560, on leukocyte haptokinesis and haptotaxis in vivo and in vitro.

Results

NSAID induced an immediate inhibiting effect on leukocyte migration both in vitro and in vivo. This effect was dose-dependent and was not restricted to a specific type of leukocytes. The inhibition of leukocyte migration by NSAID was partially re-stored after removal of inhibiting agent. Only complete blockade of leukocyte migration was accompanied by a strong reduction of [Ca2+]i.

Conclusions

NSAID strongly supress leukocyte migration. The results of the present study may have important clinical implications since blockade of leukocyte migration can be achieved after topical application of NSAID.
Clinical benefit of gluten-free diet in screen-detected older celiac disease patients
Authors: Vilppula Anitta , Kaukinen Katri , Luostarinen Liisa , Krekelä Ilkka , Patrikainen Heikki , Valve Raisa , Luostarinen Markku , Laurila Kaija , Mäki Markku , Collin Pekka
Published: December 2011

Background

The utility of serologic screening for celiac disease is still debatable. Evidence suggests that the disorder remains undetected even in the older population. It remains obscure whether screening makes good or harm in subjects with long-standing gluten ingestion. We evaluated whether older subjects benefit from active detection and subsequent gluten free dietary treatment of celiac disease.

Methods

Thirty-five biopsy-proven patients aged over 50 years had been detected by serologic mass screening. We examined the disease history, dietary compliance, symptoms, quality of life and bone mineral density at baseline and 1-2 years after the commencement of a gluten-free diet. Symptoms were evaluated by gastrointestinal symptom rating scale and quality of life by psychological general well-being questionnaires. Small bowel biopsy, serology, laboratory parameters assessing malabsorption, and bone mineral density were investigated.

Results

Dietary compliance was good. The patients had initially low mean serum ferritin values indicating subclinical iron deficiency, which was restored by a gluten-free diet. Vitamin B12, vitamin D and erythrocyte folic acid levels increased significantly on diet. Celiac patients had a history of low-energy fractures more often than the background population, and the diet had a beneficial effect on bone mineral density. Alleviation in gastrointestinal symptoms was observed, even though the patients reported no or only subtle symptoms at diagnosis. Quality of life remained unchanged. Of all the cases, two thirds would have been diagnosed even without screening if the family history, fractures or concomitant autoimmune diseases had been taken carefully into account.

Conclusions

Screen-detected patients benefited from a gluten-free diet. We encourage a high index of suspicion and active case-finding in celiac disease as an alternative to mass screening in older patients.
Non-invasive ventilation (NIV) as an aid to rehabilitation in acute respiratory disease
Authors: Dyer Fran , Flude Lizzie , Bazari Farid , Jolley Caroline , Englebretsen Catherine , Lai Dilys , Polkey Michael I , Hopkinson Nicholas S
Published: December 2011

Background

Non-invasive ventilation (NIV) can increase exercise tolerance, reduce exercise induced desaturation and improve the outcome of pulmonary rehabilitation in patients with chronic respiratory disease. It is not known whether it can be applied to increase exercise capacity in patients admitted with non-hypercapnic acute exacerbations of COPD (AECOPD). We investigated the acceptability and feasibility of using NIV for this purpose.

Methods

On a single occasion, patients admitted with an acute exacerbation of chronic respiratory disease who were unable to cycle for five minutes at 20 watts attempted to cycle using NIV and their endurance time (Tlim) was recorded. To determine feasibility of this approach in clinical practice patients admitted with AECOPD were screened for participation in a trial of regular NIV assisted rehabilitation during their hospital admission.

Results

In 12 patients tested on a single occasion NIV increased Tlim from 184(65) seconds to 331(229) seconds (p = 0.04) and patients desaturated less (median difference = 3.5%, p = 0.029). In the second study, 60 patients were admitted to hospital during a three month period of whom only 18(30)% were eligible to participate and of these patients, only four (7%) consented to participate.

Conclusion

NIV improves exercise tolerance in patients with acute exacerbations of chronic respiratory disease but the applicability of this approach in routine clinical practice may be limited.

Trial registration

http://www.controlled-trials.com/ISRCTN35692743
Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: a qualitative study
Authors: Barnett Julie , Vasileiou Konstantina , Djemil Fayika , Brooks Laurence , Young Terry
Published: December 2011

Background

Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion.

Methods

A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed.

Results

Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts.

Conclusions

A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.
Association of sub-microscopic malaria parasite carriage with transmission intensity in north-eastern Tanzania
Authors: Manjurano Alphaxard , Okell Lucy , Lukindo Tedson , Reyburn Hugh , Olomi Raimos , Roper Cally , Clark Taane G , Joseph Sarah , Riley Eleanor M , Drakeley Chris
Published: December 2011

Background

In malaria endemic areas, individuals are frequently asymptomatic and may be undetected by conventional microscopy or newer, rapid diagnostic tests. Molecular techniques allow a more accurate assessment of this asymptomatic parasite burden, the extent of which is important for malaria control. This study examines the relative prevalence of sub-microscopic level parasite carriage and clonal complexity of infections (multiplicity of infection) over a range of endemicities in a region of north-eastern Tanzania where altitude is an established proxy of malaria transmission. The PCR prevalence was then compared against other measures of transmission intensity collected in the same area.

Methods

This study used 1,121 blood samples collected from a previously conducted cross-sectional malario-metric survey during the short rainy season in 2001 from 13 villages (three at < 600 m, four at 600-1,200 m and six at > 1,200 m in altitude above sea level). Samples were analysed by PCR for carriage of parasites and multiplicity of infection. These data were compared with other measures of transmission intensity collected from the same area.

Results

Parasite prevalence was 34.7% by PCR and 13.6% by microscopy; a 2.5-fold difference in line with other recent observations. This fold difference was relatively consistent at the different altitude bands despite a marked decrease in parasite prevalence with altitude: < 600 m 70.9 vs 28.6, 600-1,200 m 35.5 vs 9.9, > 1,200 m 15.8 vs 5.9. The difference between parasite prevalence by PCR was 3.2 in individuals aged between 15 and 45 years (34.5 vs 10.9) compared with 2.5 in those aged 1-5 (34.0 vs 13.5) though this was not statistically significant. Multiplicity of infection (MOI) ranged from 1.2 to 3.7 and was positively associated with parasite prevalence assessed by both PCR and microscopy. There was no association of MOI and age.

Village level PCR parasite prevalence was strongly correlated with altitude, sero-conversion rate and predicted entomological inoculation rate.

Conclusions

Asymptomatic, low density, multi-clone malaria infection was common in this study area. These infections are important as potential contributors to the infectious reservoir of parasites and need to be identified by control programmes especially in this era where malaria elimination is a focus. High throughput standardized PCR approaches are needed to identify individuals who are malaria carriers.
Apolipoprotein E expression is elevated by interleukin 1 and other interleukin 1-induced factors
Authors: Liu Ling , Aboud Orwa , Jones Richard A , Mrak Robert E , Griffin W Sue T , Barger Steven W
Published: December 2011

Background

We have previously outlined functional interactions, including feedback cycles, between several of the gene products implicated in the pathogenesis of Alzheimer's disease. A number of Alzheimer-related stressors induce neuronal expression of apolipoprotein E (ApoE), β-amyloid precursor protein (βAPP), and fragments of the latter such as amyloid β-peptide (Aβ) and secreted APP (sAPP). These stressors include interleukin-1 (IL-1)-mediated neuroinflammation and glutamate-mediated excitotoxicity. Such circumstances are especially powerful when they transpire in the context of an APOE ε4 allele.

Methods

Semi-quantitative immunofluorescence imaging was used to analyze rat brains implanted with IL-1β slow-release pellets, sham pellets, or no pellets. Primary neuronal or NT2 cell cultures were treated with IL-1β, glutamate, Aβ, or sAPP; relative levels of ApoE mRNA and protein were measured by RT-PCR, qRT-PCR, and western immunoblot analysis. Cultures were also treated with inhibitors of multi-lineage kinases--in particular MAPK-p38 (SB203580), ERK (U0126), or JNK (SP600125)--prior to exposure of cultures to IL-1β, Aβ, sAPP, or glutamate.

Results

Immunofluorescence of tissue sections from pellet-implanted rats showed that IL-1β induces expression of βAPP, IL-1α, and ApoE; the latter was confirmed by western blot analysis. These protein changes were mirrored by increases in their mRNAs, as well as in those encoding IL-1β, IL-1β-converting enzyme (ICE), and tumor necrosis factor (TNF). IL-1β also increased ApoE expression in neuronal cultures. It stimulated release of sAPP and glutamate in these cultures too, and both of these agents--as well as Aβ--stimulated ApoE expression themselves, suggesting that they may contribute to the effect of IL-1β on ApoE levels. Inhibitors of MAPK-p38, ERK, and JNK inhibited ApoE induction by all these agents except glutamate, which was sensitive only to inhibitors of ERK and JNK.

Conclusion

Conditions of glial activation and hyperexcitation can elevate proinflammatory cytokines, ApoE, glutamate, βAPP, and its secreted fragments. Because each of these factors promotes glial activation and neuronal hyperexcitation, these relationships have the potential to sustain self-propagating neurodegenerative cycles that could culminate in a progressive neurodegenerative disorder such as Alzheimer's disease.
Neuroprotective response after photodynamic therapy: Role of vascular endothelial growth factor
Authors: Suzuki Misa , Ozawa Yoko , Kubota Shunsuke , Hirasawa Manabu , Miyake Seiji , Noda Kousuke , Tsubota Kazuo , Kadonosono Kazuaki , Ishida Susumu
Published: December 2011

Background

Anti-vascular endothelial growth factor (VEGF) drugs and/or photodynamic therapy (PDT) constitute current treatments targeting pathological vascular tissues in tumors and age-related macular degeneration. Concern that PDT might induce VEGF and exacerbate the disease has led us to current practice of using anti-VEGF drugs with PDT simultaneously. However, the underlying molecular mechanisms of these therapies are not well understood.

Methods

We assessed VEGF levels after PDT of normal mouse retinal tissue, using a laser duration that did not cause obvious tissue damage. To determine the role of PDT-induced VEGF and its downstream signaling, we intravitreally injected a VEGF inhibitor, VEGFR1 Fc, or a PI3K/Akt inhibitor, LY294002, immediately after PDT. Then, histological and biochemical changes of the retinal tissue were analyzed by immunohistochemistry and immunoblot analyses, respectively.

Results

At both the mRNA and protein levels, VEGF was upregulated immediately and transiently after PDT. VEGF suppression after PDT resulted in apoptotic destruction of the photoreceptor cell layer in only the irradiated area during PDT. Under these conditions, activation of the anti-apoptotic molecule Akt was suppressed in the irradiated area, and levels of the pro-apoptotic protein BAX were increased. Intravitreal injection of a PI3K/Akt inhibitor immediately after PDT increased BAX levels and photoreceptor cell apoptosis.

Conclusion

Cytotoxic stress caused by PDT, at levels that do not cause overt tissue damage, induces VEGF and activates Akt to rescue the neural tissue, suppressing BAX. Thus, the immediate and transient induction of VEGF after PDT is neuroprotective.
Sequencing and characterization of Varicella-Zoster virus vaccine strain SuduVax
Authors: Kim Jong Ik , Jung Gyoo Seung , Kim Yu Young , Ji Ga Young , Kim Hyung Seok , Wang Wen Dan , Park Ho Sun , Park Song Yong , Kim Geun Hee , Kwon Shi Nae , Lee Keon Myung , Ahn Jin Hyun , Yoon Yeup , Lee Chan Hee
Published: December 2011

Background

Varicella-zoster virus (VZV) causes chickenpox in children and shingles in older people. Currently, live attenuated vaccines based on the Oka strain are available worldwide. In Korea, an attenuated VZV vaccine has been developed from a Korean isolate and has been commercially available since 1994. Despite this long history of use, the mechanism for the attenuation of the vaccine strain is still elusive. We attempted to understand the molecular basis of attenuation mechanism by full genome sequencing and comparative genomic analyses of the Korean vaccine strain SuduVax.

Results

SuduVax was found to contain a genome that was 124,759 bp and possessed 74 open reading frames (ORFs). SuduVax was genetically most close to Oka strains and these Korean-Japanese strains formed a strong clade in phylogenetic trees. SuduVax, similar to the Oka vaccine strains, underwent T- > C substitution at the stop codon of ORF0, resulting in a read-through mutation to code for an extended form of ORF0 protein. SuduVax also shared certain deletion and insertion mutations in ORFs 17, 29, 56 and 60 with Oka vaccine strains and some clinical strains.

Conclusions

The Korean VZV vaccine strain SuduVax is genetically similar to the Oka vaccine strains. Further comparative genomic and bioinformatics analyses will help to elucidate the molecular basis of the attenuation of the VZV vaccine strains.
Expression of the Dopaminergic D1 and D2 Receptors in the Anterior Cingulate Cortex in a Model of Neuropathic Pain
Authors: Ortega-Legaspi J Manuel , de Gortari Patricia , Garduño-Gutiérrez René , Amaya María Isabel , León-Olea Martha , Coffeen Ulises , Pellicer Francisco
Published: December 2011

Background:

The anterior cingulate cortex (ACC) has been related to the affective component of pain. Dopaminergic mesocortical circuits, including the ACC, are able to inhibit neuropathic nociception measured as autotomy behaviour. We determined the changes in dopamine D1 and D2 (D1R and D2R) receptor expression in the ACC (cg1 and cg2) in an animal model of neuropathic pain. The neuropathic group had noxious heat applied in the right hind paw followed 30 min. later by right sciatic denervation. Autotomy score (AS) was recorded for eight days and subsequently classified in low, medium and high AS groups. The control consisted of naïve animals. A semiquantitative RT-PCR procedure was done to determine mRNA levels for D1R and D2R in cg1 and cg2, and protein levels were measured by Western Blot.

Results:

The results of D1R mRNA in cg1 showed a decrease in all groups. D2R mRNA levels in cg1 decreased in low AS and increased in medium and high AS. Regarding D1R in cg2, there was an increase in all groups. D2R expression levels in cg2 decreased in all groups. In cg1, the D2R mRNA correlated positively with autotomy behaviour. Protein levels of D2R in cg1 increased in all groups but to a higher degree in low AS. In cg2 D2R protein only decreased discretely. D1R protein was not found in either ACC region.

Conclusions:

This is the first evidence of an increase of inhibitory dopaminergic receptor (D2R) mRNA and protein in cg1 in correlation with nociceptive behaviour in a neuropathic model of pain in the rat.
Comparison of intestinal parasitic infection in newly arrived and resident workers in Qatar
Authors: Abu-Madi Marawan A , Behnke Jerzy M , Ismail Ahmed , Al-Olaqi Nada , Al-Zaher Kefah , El-Ibrahim Roda
Published: December 2011

Background

The rapid growth of Qatar in the last two decades has been associated with an enormous expansion of building programs in its cities and in the provision of new service industries. This in turn has attracted a large influx of immigrant workers seeking employment in jobs associated with food handling, domestic service and the building industry. Many of these immigrants come from countries in the tropics and subtropics where intestinal parasitic infections are common.

Methods

We analyzed intestinal parasitic infections recorded in 2008 among immigrant and long-term resident workers in Doha city, Qatar (n = 1538). Stool examinations were carried out at the Hamad Medical Corporation and at the Medical Commission in Doha using standard procedures.

Results

Overall, 21.5% of subjects were infected with at least one of the species recorded (8 helminth and 4 protozoan species; the highest prevalence was for hookworms = 8.3%) and there were strong regional effects on prevalence of helminths, with subjects from North East Africa and Nepal showing particularly high prevalence. Most helminths declined in prevalence in subjects that acquired residency status in Qatar, especially among female subjects, but there was a marked exception among male Nepalese workers, who continued to harbour helminth infections (notably hookworms) after they became residents. Contrary to all other regional groups the prevalence of Giardia duodenalis was higher among Nepalese residents compared with new arrivals, while Blastocystis hominis infections were more common among residents of all regions, and especially among North East Africans.

Conclusions

Our analysis has identified male Nepalese workers as a particular risk group continuing to harbour hookworm infection and G. duodenalis as residents, and subjects from North East Africa are as particularly likely to acquire B. hominis infection after settling in the country. These conclusions have important implications for the health authorities in Qatar.
A novel inhibitor of fatty acid synthase shows activity against HER2+ breast cancer xenografts and is active in anti-HER2 drug-resistant cell lines
Authors: Puig Teresa , Aguilar Helena , Cufí Sílvia , Oliveras Glòria , Turrado Carlos , Ortega-Gutiérrez Sílvia , Benhamú Bellinda , López-Rodríguez María Luz , Urruticoechea Ander , Colomer Ramon
Published: December 2011

Introduction

Inhibiting the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of breast carcinoma cells, and this is linked to human epidermal growth factor receptor 2 (HER2) signaling pathways in models of simultaneous expression of FASN and HER2.

Methods

In a xenograft model of breast carcinoma cells that are FASN+ and HER2+, we have characterised the anticancer activity and the toxicity profile of G28UCM, the lead compound of a novel family of synthetic FASN inhibitors. In vitro, we analysed the cellular and molecular interactions of combining G28UCM with anti-HER drugs. Finally, we tested the cytotoxic ability of G28UCM on breast cancer cells resistant to trastuzumab or lapatinib, that we developed in our laboratory.

Results

In vivo, G28UCM reduced the size of 5 out of 14 established xenografts. In the responding tumours, we observed inhibition of FASN activity, cleavage of poly-ADPribose polymerase (PARP) and a decrease of p-HER2, p- protein kinase B (AKT) and p-ERK1/2, which were not observed in the nonresponding tumours. In the G28UCM-treated animals, no significant toxicities occurred, and weight loss was not observed. In vitro, G28UCM showed marked synergistic interactions with trastuzumab, lapatinib, erlotinib or gefitinib (but not with cetuximab), which correlated with increases in apoptosis and with decreases in the activation of HER2, extracellular signal-regulated kinase (ERK)1/2 and AKT. In trastuzumab-resistant and in lapatinib-resistant breast cancer cells, in which trastuzumab and lapatinib were not effective, G28UCM retained the anticancer activity observed in the parental cells.

Conclusions

G28UCM inhibits fatty acid synthase (FASN) activity and the growth of breast carcinoma xenografts in vivo, and is active in cells with acquired resistance to anti-HER2 drugs, which make it a candidate for further pre-clinical development.
A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery - the FOCCUS study
Authors: Cuthbertson Brian H , Campbell Marion K , Stott Stephen A , Elders Andrew , Hernández Rodolfo , Boyers Dwayne , Norrie John , Kinsella John , Brittenden Julie , Cook Jonathan , Rae Daniela , Cotton Seonaidh C , Alcorn David , Addison Jennifer , Grant Adrian ,   the FOCCUS study group
Published: December 2011

Introduction

Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery.

Methods

This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome.

Results

A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective.

Conclusions

Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care.

Trial registration

Prospective Clinical Trials, ISRCTN32188676
Asymptotics of geometrical navigation on a random set of points in the plane
Authors: Bonichon Nicolas , Marckert Jean-François
Published: December 2011

A navigation on a set of points S is a rule for choosing which point to move to from the present point in order to progress toward a specified target. We study some navigations in the plane where S is a nonuniform Poisson point process (in a finite domain) with intensity going to +∞. We show the convergence of the traveller's path lengths, and give the number of stages and the geometry of the traveller's trajectories, uniformly for all starting points and targets, for several navigations of geometric nature. Other costs are also considered. This leads to asymptotic results on the stretch factors of random Yao graphs and random θ-graphs.
Topological relationships in spatial tessellations
Authors: Weiss Viola , Cowan Richard
Published: December 2011

Tessellations of R3 that use convex polyhedral cells to fill the space can be extremely complicated. This is especially so for tessellations which are not ‘facet-to-facet’, that is, for those where the facets of a cell do not necessarily coincide with the facets of that cell's neighbours. Adjacency concepts between neighbouring cells (or between neighbouring cell elements) are not easily formulated when facets do not coincide. In this paper we make the first systematic study of these topological relationships when a tessellation of R3 is not facet-to-facet. The results derived can also be applied to the simpler facet-to-facet case. Our study deals with both random tessellations and deterministic ‘tilings’. Some new theory for planar tessellations is also given.
Infinite level-dependent QBD processes and matrix-analytic solutions for stochastic chemical kinetics
Authors: Dayar Tuğrul , Sandmann Werner , Spieler David , Wolf Verena
Published: December 2011

Systems of stochastic chemical kinetics are modeled as infinite level-dependent quasi-birth-and-death (LDQBD) processes. For these systems, in contrast to many other applications, levels have an increasing number of states as the level number increases and the probability mass may reside arbitrarily far away from lower levels. Ideas from Lyapunov theory are combined with existing matrix-analytic formulations to obtain accurate approximations to the stationary probability distribution when the infinite LDQBD process is ergodic. Results of numerical experiments on a set of problems are provided.
Threshold behaviour of emerging epidemics featuring contact tracing
Authors: Ball Frank G. , Knock Edward S. , O'Neill Philip D.
Published: December 2011

This paper is concerned with a stochastic model for the spread of an epidemic with a contact tracing scheme, in which diagnosed individuals may name some of their infectious contacts, who are then removed if they have not been already. Traced individuals may or may not also be asked to name their own contacts. The epidemic is studied by considering an approximating, modified birth-death process with intersibling dependencies, for which a threshold parameter and expressions from which extinction probabilities may be calculated are derived. When all individuals can name their contacts, it is shown that this threshold parameter depends on the infectious period distribution only through its mean. Numerical studies show that the infectious period distribution choice can have a material effect on the threshold behaviour of an epidemic, while the dependencies help reduce spread.
Asymptotic inference for partially observed branching processes
Authors: Kvitkovičová Andrea , Panaretos Victor M.
Published: December 2011

We consider the problem of estimation in a partially observed discrete-time Galton-Watson branching process, focusing on the first two moments of the offspring distribution. Our study is motivated by modelling the counts of new cases at the onset of a stochastic epidemic, allowing for the facts that only a part of the cases is detected, and that the detection mechanism may affect the evolution of the epidemic. In this setting, the offspring mean is closely related to the spreading potential of the disease, while the second moment is connected to the variability of the mean estimators. Inference for branching processes is known for its nonstandard characteristics, as compared with classical inference. When, in addition, the true process cannot be directly observed, the problem of inference suffers significant further perturbations. We propose nonparametric estimators related to those used when the underlying process is fully observed, but suitably modified to take into account the intricate dependence structure induced by the partial observation and the interaction scheme. We show consistency, derive the limiting laws of the estimators, and construct asymptotic confidence intervals, all valid conditionally on the explosion set.
A Generalized Coupon Collector Problem
Authors: Xu Weiyu , Tang A. Kevin
Published: December 2011

This paper presents an analysis of a generalized version of the coupon collector problem, in which the collector receives d coupons each run and chooses the least-collected coupon so far. In the asymptotic case when the number of coupons n goes to infinity, we show that, on average, (nlogn) / d + (n / d)(m − 1)log logn + O(mn) runs are needed to collect m sets of coupons. An exact algorithm is also developed for any finite case to compute the exact mean number of runs. Numerical examples are provided to verify our theoretical predictions.
The answer is 17 years, what is the question: understanding time lags in translational research
Authors: Morris Zoë Slote , Wooding Steven , Grant Jonathan
Published: December 2011

This study aimed to review the literature describing and quantifying time lags in the health research translation process. Papers were included in the review if they quantified time lags in the development of health interventions. The study identified 23 papers. Few were comparable as different studies use different measures, of different things, at different time points. We concluded that the current state of knowledge of time lags is of limited use to those responsible for R&D and knowledge transfer who face difficulties in knowing what they should or can do to reduce time lags. This effectively ‘blindfolds’ investment decisions and risks wasting effort. The study concludes that understanding lags first requires agreeing models, definitions and measures, which can be applied in practice. A second task would be to develop a process by which to gather these data.
Doctors recognized by the British honours systems: A retrospective analysis of the last decade
Authors: Islam Shofiq , Cole Jennifer L , Taylor Christopher J
Published: December 2011

Objectives

The British honours system is one of the oldest in the world rewarding individuals, including those of the medical profession. The authors were interested to see if any particular specialty was honoured to a greater extent. We aimed to establish the number of those honoured, the duration of clinical practice involved, as well as additional factors.

Design

A retrospective analysis of doctors receiving honours (Knight/Dame, CBE, OBE, MBE) in the last decade was performed.

Setting

UK-registered doctors.

Participants

Doctors were identified from publicly available listings.

Main outcome measures

Demographics of all honoured doctors, including number of years of service, specialty affiliation and the number of recipients holding professorial status were collected. Clinicians were stratified into four subgroups: General Practitioners, Physicians, Surgeons and Others. Data were analysed using parametric statistical tests.

Results

Four hundred and seventeen doctors were identified. Four hundred and two clinicians had a documented subspecialty affiliation. Of the 402: GPs ( n = 142), Physicians ( n = 100), Surgeons ( n = 34) and Others ( n = 126). The number of years in clinical practice from registration to conference of honours was significantly shorter for GPs when compared to hospital-based specialties ( P < 0.05). The top 10 specialties of individuals honoured are tabulated. Professors constituted 30% ( n = 131) of those honoured. These individuals were sub-divided according to specialty affiliation with a significant difference observed ( P < 0.05).

Conclusions

The most honoured specialty was General Practice. However, when corrected for total subspecialty population, the number one ranking specialty was Public Health Medicine. Academic clinicians are well represented. The findings may be of interest to the medical community.
Properties and units in the clinical laboratory sciences. Part XXIII. The NPU terminology, principles, and implementation: A user’s guide (IUPAC Technical Report)
Authors: Petersen Ulla Magdal , Dybkær René , Olesen Henrik
Published: December 2011

This document describes the application of the syntax, semantic rules, and format of the Nomenclature for Properties and Units (NPU) terminology for coded dedicated kinds-of-property in the various subject fields of the clinical laboratory sciences. The document sums up considerations and reasoning by the Committee and Subcommittee on Nomenclature for Properties and Units (C-SC-NPU) and collects the experience with the system through some eight years of application in electronic health communication. Access to the NPU terminology in English is currently at , via the English download files from the Danish Release Centre under the National Board of Health. Updates to the terminology are usually presented once a month.
Consumer Participation in Coproduction: “I Made it Myself” Effects on Consumers’ Sensory Perceptions and Evaluations of Outcome and Input Product
Authors: Troye Sigurd Villads , Supphellen Magne
Published: December 2011

Consumers engage in self-production when they play an active role in the creation of end products, such as preparing a meal or assembling a piece of furniture. In three experimental studies of self-production involving a branded input product, the authors show that consumers’ active engagement in the value creation process (preparing a meal) positively biases their evaluations of an outcome (a dish) and an input product (a dinner kit). A positive evaluation bias for the input product occurs despite increased self-attribution due to self-production. In support of an associative self-anchoring explanation and the notion of self-generated validity, self-producing consumers bias their sensory perceptions (e.g., perceived level of saltiness and spiciness) so that they match a positive evaluation of the outcome. Mediation analyses show that perceived self-integration (perceived link between self and outcome) partly mediates the positive effect of self-production on outcome evaluation. The authors conclude that branded input products may benefit from the evaluation bias caused by self-production.
Sawdust Ash Stabilization of Reclaimed Asphalt Pavement
Authors: Osinubi Kolawole J. , Edeh Joseph E. , Onoja Williams O.
Published: December 2011

Pavement rehabilitation and reconstruction generates large volume of reclaimed asphalt pavements (RAP) aggregates. Also, large quantities of sawdust are generated by logging industries worldwide. This paper presents results of the laboratory evaluation of the characteristics of sawdust ash (SDA) stabilized RAP with a view to determine its suitability for use as subbase and base material in flexible pavements. The RAP-SDA mixtures were subjected to British standard light (BSL) (standard Proctor) compactive effort to determine the compaction characteristics and California bearing ratio (CBR). Test results show that the properties of RAP improved with SDA treatment. The particle grading improved from 99 % coarse aggregate and 1 % fines, with AASHTO classification of A-1-a for 100 % RAP to 29–95 % coarse aggregate and 5–71 % fines, with AASHTO classification that range from A-1-a (granular materials), for the various RAP-SDA mix proportions to A-4 (silty materials) for 100 % SDA. Maximum dry density (MDD) and optimum moisture content (OMC) increased with higher SDA content in the mixes. The CBR values initially decreased with higher SDA content to a minimum value of 11 % recorded for 30%RAP/70%SDA mix and thereafter increased. With the potential of time-dependent increase in strength in view, the 90%RAP/10%SDA mix that recorded a CBR value of 26 % (soaked for 24 h) can be used as subbase material in flexible pavements. This research provides an initial lead to the evaluation of SDA stabilized RAP as highway construction material, as it is based on CBR determination, a limited parameter that does not provide information concerning all important solicitations that bases and subbases are subjected to. Further work may be encouraged to assess resilient modulus of this material under cyclic load, as well as the assessment of permanent deformation of SDA stabilized RAP. Insignificant expansion and insignificant water absorption were observed.