Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is frequently associated with cognitive and motor dysfunction. We analyzed cerebrospinal fluid from 32 cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex using a 51-plex cytokine assay. Group-specific differences were found for the majority of analytes with an increase in cases of CCL11 (eotaxin), a chemokine involved in eosinophil recruitment. Network analysis revealed an inverse relationship between interleukin 1 receptor antagonist and colony-stimulating factor 1, colony-stimulating factor 2 and interleukin 17F, without effects on interleukin 1α or interleukin 1ß, suggesting a disturbance in interleukin 1 signaling. Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity.

Multiple-strain colonization in nasal carriers of Staphylococcus aureus.

Staphylococcus aureus is a commensal that can also cause invasive infection. Reports suggest that nasal cocolonization occurs rarely, but the resources required to sequence multiple colonies have precluded its large-scale investigation. A staged protocol was developed to maximize detection of mixed-spa-type colonization while minimizing laboratory resources using 3,197 S. aureus-positive samples from a longitudinal study of healthy individuals in Oxfordshire, United Kingdom. Initial typing of pooled material from each sample identified a single unambiguous strain in 89.6% of samples. Twelve single-colony isolates were typed from samples producing ambiguous initial results. All samples could be resolved into one or more spa types using the protocol. Cocolonization point prevalence was 3.4 to 5.8% over 24 months of follow-up in 360 recruitment-positives. However, 18% were cocolonized at least once, most only transiently. Cocolonizing spa types were completely unrelated in 56% of samples. Of 272 recruitment-positives returning ≥12 swabs, 166 (61%) carried S. aureus continuously but only 106 (39%) carried the same single spa type without any cocolonization; 31 (11%) switched spa type and 29 (11%) had transient cocarriage. S. aureus colonization is dynamic even in long-term carriers. New unrelated cocolonizing strains could increase invasive disease risk, and ongoing within-host evolution could increase invasive potential, possibilities that future studies should explore.

Attributions and self-efficacy for physical activity in multiple sclerosis.

Self-efficacy is an important predictor of health-related physical activity in multiple sclerosis (MS). While past experiences are believed to influence efficacy beliefs, the explanations individuals provide for these experiences also may be critical. Our objective was to test the hypothesis that perceived success or failure to accumulate 150 min of physical activity in the previous week would moderate the relationship between the attributional dimension of stability and self-efficacy to exercise in the future. Forty-two adults with MS participated in this cross-sectional descriptive study. Participants completed questions assessing physical activity, perceived outcome for meeting the recommended level of endurance activity, attributions for the outcome, and exercise self-efficacy. Results from hierarchical multiple regression revealed a significant main effect for perceived outcome predicting self-efficacy that was qualified by a significant interaction. The final model, which included perceived outcome, stability, and the interaction term, predicted 37% of the variance in exercise self-efficacy, F (3, 38) = 7.27, p = .001. Our findings suggest that the best prediction of self-efficacy in the MS population may include the interaction of specific attributional dimensions with success/failure at meeting the recommended physical activity dose. Attributions may be another target for interventions aimed at increasing the physical activity in MS.

Resprouting as a key functional trait: how buds, protection and resources drive persistence after fire.

Resprouting as a response to disturbance is now widely recognized as a key functional trait among woody plants and as the basis for the persistence niche. However, the underlying mechanisms that define resprouting responses to disturbance are poorly conceptualized. Resprouting ability is constrained by the interaction of the disturbance regime that depletes the buds and resources needed to fund resprouting, and the environment that drives growth and resource allocation. We develop a buds-protection-resources (BPR) framework for understanding resprouting in fire-prone ecosystems, based on bud bank location, bud protection, and how buds are resourced. Using this framework we go beyond earlier emphases on basal resprouting and highlight the importance of apical, epicormic and below-ground resprouting to the persistence niche. The BPR framework provides insights into: resprouting typologies that include both fire resisters (i.e. survive fire but do not resprout) and fire resprouters; the methods by which buds escape fire effects, such as thick bark; and the predictability of community assembly of resprouting types in relation to site productivity, disturbance regime and competition. Furthermore, predicting the consequences of global change is enhanced by the BPR framework because it potentially forecasts the retention or loss of above-ground biomass.

Transmission and control in an institutional pandemic influenza A(H1N1) 2009 outbreak.

A pandemic influenza A(H1N1) 2009 outbreak in a summer school affected 117/276 (42%) students. Residential social contact was associated with risk of infection, and there was no evidence for transmission associated with the classroom setting. Although the summer school had new admissions each week, which provided susceptible students the outbreak was controlled using routine infection control measures (isolation of cases, basic hygiene measures and avoidance of particularly high-risk social events) and prompt treatment of cases. This was in the absence of chemoprophylaxis or vaccination and without altering the basic educational activities of the school. Modelling of the outbreak allowed estimation of the impact of interventions on transmission. These models and follow-up surveillance supported the effectiveness of routine infection control measures to stop the spread of influenza even in this high-risk setting for transmission.

Nonequilibrium band mapping of unoccupied bulk states below the vacuum level by two-photon photoemission.

We demonstrate angle-resolved, tunable, two-photon photoemission (2PPE) to map a bulk unoccupied band, viz. the Cu sp band 0 to 1 eV below the vacuum level, in the vicinity of the L point. This short-lived bulk band is seen due to the strong optical pump rate, and the observed transition energies and their dispersion with photon energy ℏω, are in excellent agreement with tight-binding band-structure calculations. The variation of the final-state energy with ℏω has a measured slope of ∼1.64 in contrast to values of 1 or 2 observed for 2PPE from two-dimensional states. This unique variation illustrates the significant role of the perpendicular momentum ℏk_{⊥} in 2PPE.

'Feral' and 'wild'-type methicillin-resistant Staphylococcus aureus in the United Kingdom.

Circulation of methicillin-resistant Staphylococcus aureus (MRSA) outside hospitals could alter the impact of hospital-based control strategies. We investigated two groups of cases (each matched to controls with MRSA): 61 'community cases' not in acute hospital in the year before MRSA isolation; and 21 cases with ciprofloxacin-sensitive (CipS) MRSA. Multi-locus sequence typing, spa-typing and Panton-Valentine leukocidin gene testing were performed and demographics obtained. Additional questionnaires were completed by community case GPs. Community cases comprised 6% of Oxfordshire MRSA. Three community cases had received no regular healthcare or antibiotics: one was infected with CipS. Ninety-one percent of community cases had healthcare-associated sequence type (ST)22/36; CipS MRSA cases had heterogeneous STs but many had recent healthcare exposure. A substantial minority of UK MRSA transmission may occur outside hospitals. Hospital strains are becoming 'feral' or persisting in long-term carriers in the community with regular healthcare contacts; those with recent healthcare exposure may nevertheless acquire non-hospital epidemic MRSA strains in the community.

HIV associated pulmonary emphysema: a review of the literature and inquiry into its mechanism.

Chronic lung diseases are increasingly recognised complications of the human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). Of these, pulmonary emphysema, characterised by permanent destruction of the lung parenchyma distal to the terminal bronchioles accompanied by various degrees of inflammation, is emerging as a distinct source of morbidity for patients infected with HIV. Similarly, HIV is now frequently cited as a susceptibility factor for the development of emphysema, independent of cigarette smoking status. The presence of common coexistent confounding factors that may predispose patients to chronic lung injury such as drugs, opportunistic infections and malnutrition, limits the scope of studies of direct mechanisms involved in HIV associated emphysematous lung disease. We review the clinical studies supporting a direct association between HIV infection and emphysema. Recent developments in the basic understanding of HIV infection and emphysema are also reviewed, since they may aid in understanding the pathobiology of HIV associated emphysema. The authors emphasise how HIV infection may affect cytotoxic lymphocyte activation, lung capillary endothelial cell injury and apoptosis, sphingolipid imbalance and oxidative stress in the lung. A better understanding of the pathogenesis of HIV associated pulmonary emphysema may provide clues and therapeutic targets that have broader application in this disease, including cigarette smoke induced emphysema.

Comparison of the time required to administer three different fluke and worm combination products to commercial beef cattle at housing.

Larger livestock units, a decline in the farm labor force, animal welfare concerns, and a trend toward more selective use of drugs have increased the focus on animal handling, time management, convenience, and compliance in administering veterinary therapeutics. This study was undertaken to quantify and compare the time needed to treat commercial beef cattle with three fluke and worm combination products with different administration profiles. Young beef cattle (n = 270) weighing approximately 400 kg were allocated to batches of five, which were randomly assigned to receive ivermectin + clorsulon injection, ivermectin + closantel injection, or levamisole + triclabendazole oral drench. The mean time needed to administer ivermectin + clorsulon (single injection) to five cattle was 31 seconds, which was significantly less than the 100 seconds needed for ivermectin + closantel (two injections) and the 126 seconds needed for levamisole + triclabendazole (P < .001). Such quantitative data can allow for better planning and selection of parasiticide treatment approaches at the farm level.

Standard operating procedure for the collection of fresh frozen tissue samples.

Studies using fresh-frozen tissue samples originating from different centres, as is often the case in EORTC related translational research, can show conflicting research results due to heterogeneity in the quality of samples and associated data from each centre. The development of infrastructure for the European Human Frozen Tumour Tissue Bank (TuBaFrost) anticipated this problem and Standard Operating Procedures (SOPs) have been developed to ensure samples collected are of consistent high quality and variation in research results is minimised. The SOPs drew on the best practice standard workflows and operating procedures employed by members of the TuBaFrost Consortium and key tissue bank initiatives worldwide. It was essential to provide workable solutions that reflect the variety in infrastructure and resources at the potential collecting centres and also the fact that it is not necessary to standardise every step of the collection and storage process in order to collect high quality tissue. Hence, the TuBaFrost SOPs detail the compulsory measures that must be implemented in order to become a TuBaFrost collecting centre and also make advisory recommendations regarding the less critical factors. Accordingly, the TuBaFrost SOPs are very flexible and to illustrate this the complete SOP for collecting, freezing and storing tissue at the Erasmus MC Tissue Bank is included. These TuBaFrost SOPs could equally be applicable to centres collecting samples for EORTC related translational research studies in order to standardise sample quality and produce reliable and reproducible research results.

Multi-site and nasal swabbing for carriage of Staphylococcus aureus: what does a single nose swab predict?

BACKGROUND: Carriage of Staphylococcus aureus is a risk for infections. Targeted decolonization reduces postoperative infections but depends on accurate screening. AIM: To compare detection of S. aureus carriage in healthy individuals between anatomical sites and nurse- versus self-swabbing; also to determine whether a single nasal swab predicted carriage over four weeks. METHODS: Healthy individuals were recruited via general practices. After consent, nurses performed multi-site swabbing (nose, throat, and axilla). Participants performed nasal swabbing twice-weekly for four weeks. Swabs were returned by mail and cultured for S. aureus. All S. aureus isolates underwent spa typing. Persistent carriage in individuals returning more than three self-swabs was defined as culture of S. aureus from all or all but one self-swabs. FINDINGS: In all, 102 individuals underwent multi-site swabbing; S. aureus carriage was detected from at least one site from 40 individuals (39%). There was no difference between nose (29/102, 28%) and throat (28/102, 27%) isolation rates: the combination increased total detection rate by 10%. Ninety-nine patients returned any self-swab, and 96 returned more than three. Nasal carriage detection was not significantly different on nurse or self-swab [28/99 (74%) vs 26/99 (72%); χ2: P=0.75]. Twenty-two out of 25 participants with first self-swab positive were persistent carriers and 69/71 with first self-swab negative were not, giving high positive predictive value (88%), and very high negative predictive value (97%). CONCLUSION: Nasal swabs detected the majority of carriage; throat swabs increased detection by 10%. Self-taken nasal swabs were equivalent to nurse-taken swabs and predicted persistent nasal carriage over four weeks.

TuBaFrost 3: regulatory and ethical issues on the exchange of residual tissue for research across Europe.

The regulatory regimes for research with residual tissue and accompanying data differ widely between countries in the European Union (EU): from specific consent to opt-out or even no consent at all. This could greatly hamper research where the exchange of tissue and accompanying data has become the gold standard, like in TubaFrost. Instead of adhering to international guidelines, which have a democratic deficit, or an attempt for a new set of possible harmonising rules, TubaFrost chose to create a coordinating rule: if tissue may legitimately be used for a certain kind of research in the country where it was taken and under whose jurisdiction the patient falls, it may also be used for such research in the country where it is sent to in the context of a scientific program even if in that other country other regulations would apply for research with residual tissue taken from patients under their jurisdiction. This coordinating rule has a sound basis in EU law in general and will solve the problems related to diverging national regulatory regimes in the case of cross national research with residual tissue.

TuBaFrost 6: virtual microscopy in virtual tumour banking.

Many systems have already been designed and successfully used for sharing histology images over large distances, without transfer of the original glass slides. Rapid evolution was seen when digital images could be transferred over the Internet. Nowadays, sophisticated Virtual Microscope systems can be acquired, with the capability to quickly scan large batches of glass slides at high magnification and compress and store the large images on disc, which subsequently can be consulted through the Internet. The images are stored on an image server, which can give simple, easy to transfer pictures to the user specifying a certain magnification on any position in the scan. This offers new opportunities in histology review, overcoming the necessity of the dynamic telepathology systems to have compatible software systems and microscopes and in addition, an adequate connection of sufficient bandwidth. Consulting the images now only requires an Internet connection and a computer with a high quality monitor. A system of complete pathology review supporting bio-repositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).

TuBaFrost 1: Uniting local frozen tumour banks into a European network: an overview.

TuBaFrost is the consortium responsible for the creation of a virtual European human frozen tumour tissue bank: a collection of high quality frozen residual, accurately classified tumour tissue samples, which are stored in European cancer centres and universities. This virtual tissue bank, searchable on the internet, has rules for access and use, and a code of conduct to comply with the various legal and ethical regulations in European countries. The easy accessibility and the European scale of the bank will result in the availability of a large number of samples even of rarer tumour types. Standardisation of collection, storage and quality control throughout the network is achieved minimising inter-institutional variability. A website providing access to upload, search and request samples is a key tool of the tissue bank. The search engine makes use of virtual microscopy. An overview of the development of the European virtual frozen tissue bank infrastructure is described in this paper. The various key aspects are described in more detail in a series of articles to appear in this Journal.

TuBaFrost 2: Standardising tissue collection and quality control procedures for a European virtual frozen tissue bank network.

Tumour Bank Networking presents a great challenge for oncological research as in order to carry out large-scale, multi-centre studies with minimal intrinsic bias, each tumour bank in the network must have some fundamental similarities and be using the same standardised and validated procedures. The European Human Frozen Tumour Tissue Bank (TuBaFrost) has responded to this need by the promotion of an integrated platform of tumour banks in Europe. The operational framework for TuBaFrost has drawn upon the best practice of standard workflows and operating procedures employed by members of the TuBaFrost project and key initiatives worldwide.

TuBaFrost 4: access rules and incentives for a European tumour bank.

When designing infrastructure for a networked virtual tumour bank (samples remain at the collector institutes and sample data are collected in a searchable central database), it is apparent that this can only function properly after developing an adequate set of rules for use and access. These rules must include sufficient incentives for the tissue sample collectors to remain active within the network and maintain sufficient sample levels in the local bank. These requirements resulted in a key TuBaFrost rule, stating that the custodianship of the samples remains under the authority of the local collector. As a consequence, the samples and the decision to issue the samples to a requestor are not transferred to a large organisation but instead remain with the collector, thus allowing autonomous negotiation between collector and requestor, potential co-authorship in publications or compensation for collection and processing costs. Furthermore, it realises a streamlined cost effective network, ensuring tissue visibility and accessibility thereby improving the availability of large amounts of samples of highly specific or rare tumour types as well as providing contact opportunities for collaboration between scientists with cutting edge technology and tissue collectors. With this general purpose in mind, the rules and responsibilities for collectors, requestors and central office were generated.

TuBaFrost 5: multifunctional central database application for a European tumor bank.

Developing a tissue bank database has become more than just logically arranging data in tables combined with a search engine. Current demand for high quality samples and data, and the ever-changing legal and ethical regulations mean that the application must reflect TuBaFrost rules and protocols for the collection, exchange and use of tissue. To ensure continuation and extension of the TuBaFrost European tissue bank, the custodianship of the samples, and hence the decision over whether to issue samples to requestors, remains with the local collecting centre. The database application described in this article has been developed to facilitate this open structure virtual tissue bank model serving a large group. It encompasses many key tasks, without the requirement for personnel, hence minimising operational costs. The Internet-accessible database application enables search, selection and request submission for requestors, whereas collectors can upload and edit their collection. Communication between requestor and involved collectors is started with automatically generated e-mails.

TuBaFrost: European virtual tumor tissue banking.

TuBaFrost is a consortium responsible for the task to create a virtual European human frozen tumor tissue bank, composed of high quality frozen tumor tissue collections with corresponding accurate diagnosis stored in European cancer centers and universities, searchable on the Internet, providing rules for access and use and a code of conduct to comply with the various legal and ethical regulations in European countries. Such infrastructure would enlarge tissue availability and accessibility in large amounts of specified or even rare tumor samples. Design of an infrastructure for European residual tissue banking with the described characteristics, clear focus points emerge that can be broken down in dedicated subjects: (1) standardization and quality assurance (QA) to avoid inter-institute quality variation; (2) law and ethics enabling exchange of tissue samples possible between institutes in the different European countries, where law and ethics are characterized by a strong variability; (3) rules for access, with sufficient incentives for collectors; (4) central database application containing innovations on search and selection procedures; (5) support when needed with histology images; and (6) Internet access to search and upload, with in addition a solid website giving proper information on the procedures, intentions and activities not only to the scientific community, but also to the general public. One consortium decision, part of the incentives for collectors, had major impact on the infrastructure; custodianship over the tissues as well as the tissues stay with the collector institute. Resulting in specimens that are not given to an organization, taking decisions on participation of requests, but instead the local collected tissues stay very easy to access by the collector and allows autonomous negotiation between collector and requestor on cooperation, coauthorship in publication or compensation in costs. Thereby, improving availability of large amounts of high quality samples of a highly specified or rare tumor types and contact opportunities for cooperation with other institutes.

Virtual microscopy in virtual tumor banking.

Many systems have already been designed and successfully used for sharing histology images over large distances, without transfer of the original glass slides. Rapid evolution was seen when digital images could be transferred over the Internet. Nowadays, sophisticated virtual microscope systems can be acquired, with the capability to quickly scan large batches of glass slides at high magnification and compress and store the large images on disc, which subsequently can be consulted through the Internet. The images are stored on an image server, which can give simple, easy to transfer pictures to the user specifying a certain magnification on any position in the scan. This offers new opportunities in histology review, overcoming the necessity of the dynamic telepathology systems to have compatible software systems and microscopes and in addition, an adequate connection of sufficient bandwidth. Consulting the images now only requires an Internet connection and a computer with a high quality monitor. A system of complete pathology review supporting biorepositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).

Lung cancer mortality in workers exposed to sulfuric acid mist and other acid mists.

Mortality patterns were studied in 1,165 workers exposed to sulfuric acid mist and other acid mists (primarily hydrochloric acid mist) in steel-pickling operations. Standardized mortality ratio (SMR) analysis of the full "any acid exposure" cohort (n = 1,165), with the use of U.S. death rates as a standard, showed that lung cancer was significantly elevated, with a mortality ratio of 1.64 [95% confidence interval (CI) = 1.14-2.28, based on 35 observed deaths]. The lung cancer mortality ratio for workers exposed only to sulfuric acid (n = 722) was lower (SMR = 1.39), but further restriction to the time 20 years and more from first employment in a job with probable daily sulfuric acid exposure (approximately equal to 0.2 mg/m3) yielded a mortality ratio of 1.93 (95% CI = 1.10-3.13). An excess lung cancer risk was also seen in workers exposed to acids other than sulfuric acid (SMR = 2.24; 95% CI = 1.02-2.46). When comparison was made to other steel workers (rather than to the U.S. general population) to control for socioeconomic and life-style factors such as smoking, the largest lung cancer excess was again seen in workers exposed to acids other than sulfuric acid (SMR = 2.00; 95% CI = 1.06-3.78). Adjustment for potential differences in smoking habits showed that increased smoking was unlikely to have entirely explained the increased risk. Mortality from causes of death other than lung cancer was unremarkable, with the exception of significantly low rates for deaths due to digestive system diseases.