Using Differential Item Functioning to evaluate potential bias in a high stakes postgraduate knowledge based assessment

BACKGROUND: Fairness is a critical component of defensible assessment. Candidates should perform according to ability without influence from background characteristics such as ethnicity or sex. However, performance differs by candidate background in many assessment environments. Many potential causes of such differences exist, and examinations must be routinely analysed to ensure they do not present inappropriate progression barriers for any candidate group. By analysing the individual questions of an examination through techniques such as Differential Item Functioning (DIF), we can test whether a subset of unfair questions explains group-level differences. Such items can then be revised or removed. METHODS: We used DIF to investigate fairness for 13,694 candidates sitting a major international summative postgraduate examination in internal medicine. We compared (a) ethnically white UK graduates against ethnically non-white UK graduates and (b) male UK graduates against female UK graduates. DIF was used to test 2773 questions across 14 sittings. RESULTS: Across 2773 questions eight (0.29%) showed notable DIF after correcting for multiple comparisons: seven medium effects and one large effect. Blinded analysis of these questions by a panel of clinician assessors identified no plausible explanations for the differences. These questions were removed from the question bank and we present them here to share knowledge of questions with DIF. These questions did not significantly impact the overall performance of the cohort. Group-level differences in performance between the groups we studied in this examination cannot be explained by a subset of unfair questions. CONCLUSIONS: DIF helps explore fairness in assessment at the question level. This is especially important in high-stakes assessment where a small number of unfair questions may adversely impact the passing rates of some groups. However, very few questions exhibited notable DIF so differences in passing rates for the groups we studied cannot be explained by unfairness at the question level

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

Degenerate and Other Neutrino Mass Scenarios and Dark Matter

I discuss in this talk mainly three topics related with dark matter motivated neutrino mass spectrum and a generic issue of mass pattern, the normal versus the inverted mass hierarchies. In the first part, by describing failure of a nontrivial potential counter example, I argue that the standard 3 $\nu$ mixing scheme with the solar and the atmospheric $\Delta m^2$'s is robust. In the second part, I discuss the almost degenerate neutrino (ADN) scenario as the unique possibility of accommodating dark matter mass neutrinos into the 3 $\nu$ scheme. I review a cosmological bound and then reanalyze the constraints imposed on the ADN scenario with the new data of double beta decay experiment. In the last part, I discuss the 3 $\nu$ flavor transformation in supernova (SN) and point out the possibility that neutrinos from SN may distinguish the normal versus inverted hierarchies of neutrino masses. By analyzing the neutrino data from SN1987A, I argue that the inverted mass hierarchy is disfavored by the data

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Microfluidic device for robust generation of two-component liquid-in-air slugs with individually controlled composition

Using liquid slugs as microreactors and microvessels enable precise control over the conditions of their contents on short-time scales for a wide variety of applications. Particularly for screening applications, there is a need for control of slug parameters such as size and composition. We describe a new microfluidic approach for creating slugs in air, each comprising a size and composition that can be selected individually for each slug. Two-component slugs are formed by first metering the desired volume of each reagent, merging the two volumes into an end-to-end slug, and propelling the slug to induce mixing. Volume control is achieved by a novel mechanism: two closed chambers on the chip are initially filled with air, and a valve in each is briefly opened to admit one of the reagents. The pressure of each reagent can be individually selected and determines the amount of air compression, and thus the amount of liquid that is admitted into each chamber. We describe the theory of operation, characterize the slug generation chip, and demonstrate the creation of slugs of different compositions. The use of microvalves in this approach enables robust operation with different liquids, and also enables one to work with extremely small samples, even down to a few slug volumes. The latter is important for applications involving precious reagents such as optimizing the reaction conditions for radiolabeling biological molecules as tracers for positron emission tomography

Nano-surgery at the leukocyte–endothelial docking site

The endothelium has an important role in controlling the extravasation of leukocytes from blood to tissues. Endothelial permeability for leukocytes is influenced by transmembrane proteins that control inter-endothelial adhesion, as well as steps of the leukocyte transmigration process. In a cascade consisting of leukocyte rolling, adhesion, firm adhesion, and diapedesis, a new step was recently introduced, the formation of a docking structure or “transmigratory cup.” Both terms describe a structure formed by endothelial pseudopods embracing the leukocyte. It has been found associated with both para- and transcellular diapedesis. The aim of this study was to characterize the leukocyte–endothelial contact area in terms of morphology and cell mechanics to investigate how the endothelial cytoskeleton reorganizes to engulf the leukocyte. We used atomic force microscopy (AFM) to selectively remove the leukocyte and then analyze the underlying cell at this specific spot. Firmly attached leukocytes could be removed by AFM nanomanipulation. In few cases, this exposed 8–12 μm wide and 1 μm deep footprints, representing the cup-like docking structure. Some of them were located near endothelial cell junctions. The interaction area did not exhibit significant alterations neither morphologically nor mechanically as compared to the surrounding cell surface. In conclusion, the endothelial invagination is formed without a net depolymerization of f-actin, as endothelial softening at the site of adhesion does not seem to be involved. Moreover, there were no cases of phagocytotic engulfment, but instead the formation of a transmigratory channel could be observed

Increased deep sleep in a medication-free, detoxified female offender with schizophrenia, alcoholism and a history of attempted homicide: Case report

BACKGROUND: Psychiatric sleep research has attempted to identify diagnostically sensitive and specific sleep patterns associated with particular disorders. Both schizophrenia and alcoholism are typically characterized by a severe sleep disturbance associated with decreased amounts of slow wave sleep, the physiologically significant, refreshing part of the sleep. Antisocial behaviour with severe aggression, on the contrary, has been reported to associate with increased deep sleep reflecting either specific brain pathology or a delay in the normal development of sleep patterns. The authors are not aware of previous sleep studies in patients with both schizophrenia and antisocial personality disorder. CASE PRESENTATION: The aim of the present case-study was to characterize the sleep architecture of a violent, medication-free and detoxified female offender with schizophrenia, alcoholism and features of antisocial personality disorder using polysomnography. The controls consisted of three healthy, age-matched women with no history of physical violence. The offender's sleep architecture was otherwise very typical for patients with schizophrenia and/or alcoholism, but an extremely high amount of deep sleep was observed in her sleep recording. CONCLUSIONS: The finding strengthens the view that severe aggression is related to an abnormal sleep pattern with increased deep sleep. The authors were able to observe this phenomenon in an antisocially behaving, violent female offender with schizophrenia and alcohol dependence, the latter disorders previously reported to be associated with low levels of slow wave sleep. New studies are, however, needed to confirm and explain this preliminary finding

Identification of Key Processes that Control Tumor Necrosis Factor Availability in a Tuberculosis Granuloma

Tuberculosis (TB) granulomas are organized collections of immune cells comprised of macrophages, lymphocytes and other cells that form in the lung as a result of immune response to Mycobacterium tuberculosis (Mtb) infection. Formation and maintenance of granulomas are essential for control of Mtb infection and are regulated in part by a pro-inflammatory cytokine, tumor necrosis factor-α (TNF). To characterize mechanisms that control TNF availability within a TB granuloma, we developed a multi-scale two compartment partial differential equation model that describes a granuloma as a collection of immune cells forming concentric layers and includes TNF/TNF receptor binding and trafficking processes. We used the results of sensitivity analysis as a tool to identify experiments to measure critical model parameters in an artificial experimental model of a TB granuloma induced in the lungs of mice following injection of mycobacterial antigen-coated beads. Using our model, we then demonstrated that the organization of immune cells within a TB granuloma as well as TNF/TNF receptor binding and intracellular trafficking are two important factors that control TNF availability and may spatially coordinate TNF-induced immunological functions within a granuloma. Further, we showed that the neutralization power of TNF-neutralizing drugs depends on their TNF binding characteristics, including TNF binding kinetics, ability to bind to membrane-bound TNF and TNF binding stoichiometry. To further elucidate the role of TNF in the process of granuloma development, our modeling and experimental findings on TNF-associated molecular scale aspects of the granuloma can be incorporated into larger scale models describing the immune response to TB infection. Ultimately, these modeling and experimental results can help identify new strategies for TB disease control/therapy

MLH1 mediates PARP-dependent cell death in response to the methylating agent N-methyl-N-nitrosourea

Background:Methylating agents such as N-methyl-N-nitrosourea (MNU) can cause cell cycle arrest and death either via caspase-dependent apoptosis or via a poly(ADP-ribose) polymerase (PARP)-dependent form of apoptosis. We wished to investigate the possible role of MLH1 in signalling cell death through PARP.Methods:Fibroblasts are particularly dependent on a PARP-mediated cell death response to methylating agents. We used hTERT-immortalised normal human fibroblasts (WT) to generate isogenic MLH1-depleted cells, confirmed by quantitative PCR and western blotting. Drug resistance was measured by clonogenic and cell viability assays and effects on the cell cycle by cell sorting. Damage signalling was additionally investigated using immunostaining.Results:MLH1-depleted cells were more resistant to MNU, as expected. Despite having an intact G2/M checkpoint, the WT cells did not initially undergo cell cycle arrest but instead triggered cell death directly by PARP overactivation and nuclear translocation of apoptosis-inducing factor (AIF). The MLH1-depleted cells showed defects in this pathway, with decreased staining for phosphorylated H2AX, altered PARP activity and reduced AIF translocation. Inhibitors of PARP, but not of caspases, blocked AIF translocation and greatly decreased short-term cell death in both WT and MLH1-depleted cells. This MLH1-dependent response to MNU was not blocked by inhibitors of ATM/ATR or p53.Conclusion:These novel data indicate an important role for MLH1 in signalling PARP-dependent cell death in response to the methylating agent MNU