How do value-judgements enter model-based assessments of climate sensitivity?

Philosophers argue that many choices in science are influenced by values or have value-implications, ranging from the preference for some research method’s qualities to ethical estimation of the consequences of error. Based on the argument that awareness of values in the scientific process is a necessary first step to both avoid bias and attune science best to the needs of society, an analysis of the role of values in the physical climate science production process is provided. Model-based assessment of climate sensitivity is taken as an illustrative example; climate sensitivity is useful here because of its key role in climate science and relevance for policy, by having been the subject of several assessments over the past decades including a recent shift in assessment method, and because it enables insights that apply to numerous other aspects of climate science. It is found that value-judgements are relevant at every step of the model-based assessment process, with a differentiated role of non-epistemic values across the steps, impacting the assessment in various ways. Scrutiny of current philosophical norms for value-management highlights the need for those norms to be re-worked for broader applicability to climate science. Recent development in climate science turning away from direct use of models for climate sensitivity assessment also gives the opportunity to start investigating the role of values in alternative assessment methods, highlighting similarities and differences in terms of the role of values that encourage further study

Doświadczenia masowych otwartych kursów on-line dlia udoskonalenia systemu zarządzania e-learning ATutor

AIM: This study was carried out in patients with neuropathic pain in order to assess the analgesic effects and changes in protein biomarkers after the administration of methylene blue (MB), a diaminophenothiazine with antioxidant and anti-inflammatory properties, and with inhibitory effects on nitric oxide. MATERIALS AND METHODS: Ten patients with chronic refractory neuropathic pain were randomized to receive either MB (10 mg/mL Methylthioninium chloride) 2 mg/kg (MB group) or MB 0.02 mg/kg (control group) infused over 60 minutes. Sensory function and pain (Numerical Rating Scale) were evaluated at baseline and at 60 minutes after the start of the infusion. The patients kept a pain diary during the next 24 hours and for the following 4 days. Plasma and urinary concentrations of 8-isoprostane-prostaglandin F2α (8-iso-PGF2α) and plasma protein biomarkers prior to and after the infusions were measured with radioimmunoassay and with proximity extension assay. RESULTS: A decrease of the Numerical Rating Scale at 60 minutes in comparison with baseline was observed in the MB (P=0.047) group. The decrease was significant between the MB and the control group on the day of and day after MB infusion (P=0.04 and P=0.008, respectively). There was no difference in systemic protein expressions between groups except for prolactin (PRL) (P=0.02). Three patients demonstrated diminished dynamic mechanical allodynia. CONCLUSION: MB decreased the pain levels in patients with chronic therapy-resistant neuropathic pain on the first 2 days after administration. Known as an endocrine modulator on the anterior pituitary gland, MB infusion produced a decrease of PRL. The detailed role of PRL effects in chronic neuropathic pain remains undetermined

The ‘T-Shaped Buyer’: a transactional perspective on supply chain relationships

This paper challenges the normative view of interdependent buyer-seller relationships and provides a more holistic perspective of the contextual reality that shapes buyer behaviour. By proposing an innovative qualitative methodology, which focusses on boundary-spanning, pre-sales interactions, the research penetrates complex and commercially sensitive buyer-seller relationships. The longitudinal research design uses web-based diaries and follow-up interviews to explore conditions of power based interdependence between buyers and sellers. The ensuing data is mapped using qualitative content analysis and the results are aggregated graphically for assessment. Using this approach the study develops a nuanced view of the dominant patterns of buyer behaviour, and challenges the opinion that a search for competitive advantage will strengthen cooperative relationships in conditions of power based interdependence. The paper introduces the metaphor of the 'T-Shaped Buyer' to explain the empirical findings and, while acknowledging the contextual limits of the study, suggests that this metaphor may cause both academics and practitioners to reflect on normative thinking

Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of <i>Plasmodium falciparum</i> into human erythrocytes

An effective vaccine is a priority for malaria control and elimination. The leading candidate in the Plasmodium falciparum blood stage is PfRh5. PfRh5 assembles into trimeric complex with PfRipr and PfCyRPA in the parasite, and this complex is essential for erythrocyte invasion. In this study, we show that antibodies specific for PfRh5 and PfCyRPA prevent trimeric complex formation. We identify the EGF-7 domain on PfRipr as a neutralising epitope and demonstrate that antibodies against this region act downstream of complex formation to prevent merozoite invasion. Antibodies against the C-terminal region of PfRipr were more inhibitory than those against either PfRh5 or PfCyRPA alone, and a combination of antibodies against PfCyRPA and PfRipr acted synergistically to reduce invasion. This study supports prioritisation of PfRipr for development as part of a next-generation antimalarial vaccine

Computerâ aided detection of clustered microcalcifications in multiscale bilateral filtering regularized reconstructed digital breast tomosynthesis volume

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134920/1/mp0955.pd

Imaging Immune Surveillance of Individual Natural Killer Cells Confined in Microwell Arrays

New markers are constantly emerging that identify smaller and smaller subpopulations of immune cells. However, there is a growing awareness that even within very small populations, there is a marked functional heterogeneity and that measurements at the population level only gives an average estimate of the behaviour of that pool of cells. New techniques to analyze single immune cells over time are needed to overcome this limitation. For that purpose, we have designed and evaluated microwell array systems made from two materials, polydimethylsiloxane (PDMS) and silicon, for high-resolution imaging of individual natural killer (NK) cell responses. Both materials were suitable for short-term studies (<4 hours) but only silicon wells allowed long-term studies (several days). Time-lapse imaging of NK cell cytotoxicity in these microwell arrays revealed that roughly 30% of the target cells died much more rapidly than the rest upon NK cell encounter. This unexpected heterogeneity may reflect either separate mechanisms of killing or different killing efficiency by individual NK cells. Furthermore, we show that high-resolution imaging of inhibitory synapse formation, defined by clustering of MHC class I at the interface between NK and target cells, is possible in these microwells. We conclude that live cell imaging of NK-target cell interactions in multi-well microstructures are possible. The technique enables novel types of assays and allow data collection at a level of resolution not previously obtained. Furthermore, due to the large number of wells that can be simultaneously imaged, new statistical information is obtained that will lead to a better understanding of the function and regulation of the immune system at the single cell level

Cancer risk in hospitalised psoriasis patients: a follow-up study in Sweden

We examined overall and specific cancer risks among Swedish subjects who had been hospitalised one or more times for psoriasis. A database was created by identifying such patients from the Swedish Hospital Discharge Register and linking them with the Cancer Registry. Follow-up of patients was carried out from the last hospitalisation through 2004. A total of 15 858 patients were hospitalised for psoriasis during 1965–2004, of whom 1408 developed cancer, giving an overall standardised incidence ratios (SIRs) of 1.33. A significant excess was noted for squamous cell skin cancer, and for cancers of the upper aerodigestive tract, oesophagus, stomach, liver, pancreas, lung, kidney and bladder as well as non-Hodgkin lymphoma. Many of these may reflect the effects of alcohol drinking and tobacco smoking. Patients with multiple hospitalisations showed high risk, particularly for oesophageal (SIR 6.97) and skin (SIR 4.76) cancers