Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease state, characterised by progressive airflow limitation that is not fully reversible. Although COPD is primarily a disease of the lungs there is now an appreciation that many of the manifestations of disease are outside the lung, leading to the notion that COPD is a systemic disease. Currently, diagnosis of COPD relies on largely descriptive measures to enable classification, such as symptoms and lung function. Here the limitations of existing diagnostic strategies of COPD are discussed and systems biology approaches to diagnosis that build upon current molecular knowledge of the disease are described. These approaches rely on new 'label-free' sensing technologies, such as high-throughput surface plasmon resonance (SPR), that we also describe

Empty colon: a pitfall in the assessment of colonic transit time

We report a misleading outcome of colonic transit time (CTT) assessment in an adolescent girl with functional constipation. We found prolonged total and right segmental CTT despite high doses of oral polyethylene glycol 4000 and repeated treatment with polyethylene glycol–electrolyte solution (Klean-Prep®) by nasogastric tube. A colonoscopy aiming at disimpaction of a possible faecal mass revealed an empty colon with dozens of radio-opaque markers adhered to the colonic wall. This report shows that the result of a CTT cannot be accepted blindly. Especially the clustering of many markers within narrow margins might point at entrapment of markers in mucus against the colonic wall

Measuring the Performance of Vaccination Programs Using Cross-Sectional Surveys: A Likelihood Framework and Retrospective Analysis

Justin Lessler and colleagues describe a method that estimates the fraction of a population accessible to vaccination activities, and they apply it to measles vaccination in three African countries: Ghana, Madagascar, and Sierra Leone

Clumps and streams in the local dark matter distribution

In cold dark matter cosmological models, structures form and grow by merging of smaller units. Numerical simulations have shown that such merging is incomplete; the inner cores of halos survive and orbit as "subhalos" within their hosts. Here we report a simulation that resolves such substructure even in the very inner regions of the Galactic halo. We find hundreds of very concentrated dark matter clumps surviving near the solar circle, as well as numerous cold streams. The simulation reveals the fractal nature of dark matter clustering: Isolated halos and subhalos contain the same relative amount of substructure and both have cuspy inner density profiles. The inner mass and phase-space densities of subhalos match those of recently discovered faint, dark matter-dominated dwarf satellite galaxies and the overall amount of substructure can explain the anomalous flux ratios seen in strong gravitational lenses. Subhalos boost gamma-ray production from dark matter annihilation, by factors of 4-15, relative to smooth galactic models. Local cosmic ray production is also enhanced, typically by a factor 1.4, but by more than a factor of ten in one percent of locations lying sufficiently close to a large subhalo. These estimates assume that gravitational effects of baryons on dark matter substructure are small.Comment: 14 pages, 5 figures, to appear in Nature, includes supplementary information. Full version of Figure 1 available at http://www.ucolick.org/~diemand/vl2/fig1.pn

Feasibility and effectiveness of offering a solution-focused follow-up to employees with psychological problems or muscle skeletal pain: a randomised controlled trial

BACKGROUND: Long-term sick leave has been of concern to politicians and decision-makers in Norway for several years. In the current study we assess the feasibility and effectiveness of offering a voluntary, solution-focused follow-up to sick-listed employees. METHODS: Employees on long-term sick leave due to psychological problems or muscle skeletal pain were randomly allocated to be offered a solution-focused follow-up (n = 122) or "treatment as usual" (n = 106). The intervention was integrated within 2 social security offices' regular follow-up. The intervention group was informed about the offer with letters, telephone calls and information meetings. Feasibility was measured by rate of uptake to the intervention, and effectiveness by number of days on sick leave. RESULTS: In general, few were reached with the different information elements. While the letter was sent to all, only 31% were reached by telephone and 15% attended the information meetings. Thirteen employees (11.5%) in the intervention group participated in the solution-focused follow-up. Intention to treat analysis showed no difference in mean length of sick leave between the intervention group (217 days) and the control group (189 days) (p = 0,101). CONCLUSION: Even if the information strategy might be improved, it is not likely that a voluntary solution-focused follow-up offered by the social security offices would result in measurable reduction in length of sick leave on a population level. However, the efficacy of a solution-focused follow-up for the persons reporting a need for this approach should be further investigated

Inflammation Triggers Emergency Granulopoiesis through a Density-Dependent Feedback Mechanism

Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of “emergency” granulopoiesis that is dependent on C/EBPβ. Here, we show in mice that alum triggers emergency granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses of hematopoietic stem and progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM neutrophils, raising the possibility that HSPC responses to inflammation are an indirect result of the exhaustion of BM neutrophil stores. The induction of neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1, elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ, thought to be necessary for enhanced generative capacity of BM, is dispensable for increased proliferation of HSPC to alum or neutropenia, but plays a role in terminal neutrophil differentiation during granulopoietic recovery. We conclude that alum elicits a transient increase in G-CSF production via IL-1RI for the mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF for accelerated granulopoiesis

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

A 10 year case study on the changing determinants of University student satisfaction in the UK

Higher Education (HE), once the prerogative of a tiny elite, is now accessible to larger numbers of people around the world than ever before yet despite the fact that an understanding of student satisfaction has never been more important for today’s universities, the concept remains poorly understood. Here we use published data from the UK’s National Student Survey (NSS), representing data from 2.3 million full-time students collected from 2007 to 2016, as a case study of the benefits and limitations of measuring student satisfaction that might have applicability for other countries, particularly those that, like the UK, have experienced significant growth in student numbers. The analyses showed that the factor structure of the NSS remained generally stable and that the ability of the NSS to discriminate between different subjects at different universities actually improved over the ten-year sample period. The best predictors of overall satisfaction were 'Teaching Quality' and 'Organisation & Management', with 'Assessment & Feedback' having relatively weak predictive ability, despite the sector's tangible efforts to improve on this metric. The tripling of student fees in 2012 for English students (but not the rest of the UK) was used as a ‘natural experiment’ to investigate the sensitivity of student satisfaction ratings to the real economic costs of HE. The tuition fee increase had no identifiable negative effect, with student satisfaction steadily improving throughout the decade. Although the NSS was never designed to measure perceived value-for money, its insensitivity to major changes in the economic costs of HE to the individual suggest that the conventional concept of student satisfaction is incomplete. As such we propose that the concept of student satisfaction: (i) needs to be widened to take into account the broader economic benefits to the individual student by including measures of perceived value-for-money and (ii) should measure students’ level of satisfaction in the years post-graduation, by which time they may have a greater appreciation of the value of their degree in the workplace