New unified laws in fatigue: From the Wöhler’s to the Paris’ regime

Generalizations and unification of the celebrated Paris’ and Wöhler’s laws for fatigue crack propagation are derived by applying the recently developed quantized (or finite) fracture mechanics. In particular, three generalized Paris’, Wöhler’s or unified laws are proposed and compared, demonstrating their applicability for predicting the life time of structures containing from small (the Wöhler’s regime) to large (the Paris’ regime) propagating fatigue cracks.     

Cryptosporidium parvum initiates inflammatory bowel disease in germfree T cell receptor-alpha-deficient mice

Flora-bearing mice with targeted disruption of T cell receptor (TCR)-alpha or -beta genes spontaneously develop intestinal inflammation with features similar to ulcerative colitis in humans. TCR-alpha-deficient mice maintained germfree or colonized with a limited number of intestinal bacteria failed to develop inflammatory bowel disease (IBD)-like lesions. Evidently, inflammation in these mice does not develop spontaneously or result from a generalized antigenic stimulation, but rather requires induction by a heretofore unidentified specific stimulus. We describe the development of IBD-like lesions in germfree TCR-alpha-deficient mice monoassociated with the protozoan Cryptosporidium parvum. Lesions were seen in distal ileum, cecum, and colon and were most severe in the cecum. A prominent leukocytic infiltrate within the lamina propria was a common characteristic of the lesions observed in the C. parvum-infected germfree TCR-alpha-deficient mice. The leukocytic infiltrate was composed of aggregates of B220+ cells, the majority of which expressed surface IgD (ie, conventional B lymphocytes). It has been proposed that antigenic stimulation by a microorganism(s) is needed to initiate intestinal inflammation in TCR-alpha-deficient mice. Our results indicate that a single microbial species, C. parvum, is capable of triggering the development of IBD-like lesions in germfree TCR-alpha-deficient mice.     

Mathematical determination of feeding patterns and its consequence on correlational studies

The cell cycle regulatory proteins, which include cyclin-dependent kinases (cdks), cdk inhibitors (CKIs), cyclins, and the pRB, and E2F families of proteins, constitute a network of interacting factors which govern exit from or passage through the mammalian cell cycle. While the proteins within these families have similar structural characteristics, each family member exhibits distinct expression patterns during embryogenesis and distinct biological activities. In order to begin to understand the tissue-specific roles of these interacting factors, we determined the expression pattern and activity of the pRB, E2F, cyclin, cdk, and CKI families of cell cycle regulatory proteins during retinoic acid-induced (neuronal pathway) and DMSO-induced (cardiac muscle pathway) differentiation of the pluripotent murine embryonal carcinoma cell line, P19. We demonstrate here that P19 terminal differentiation causes lineage-specific changes in the expression and activity of distinct members of the E2F, pRB, cyclin, and CKI families. Furthermore, dynamic changes in the activities of these cell cycle regulatory proteins occur through several overlapping mechanisms, culminating in repression of DNA-binding activity by all of the E2F family members as cells terminally differentiate.     

Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing beta-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 microgram/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the 12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5 microgram/kg/d produced only minor eosinophilia, and doses of 7.5 to 20 microgram/kg were required to induce >/=1.5-fold neutrophil increments in the 3 patients who underwent dose-escalation. However, neutrophilic responses to 5 microgram/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4). In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1% +/- 8.9%; P = .042) or interleukin-3 (IL-3; 19.3% +/- 7.7%; P = .063), both of which utilize the beta-common chain of the GM-CSF receptor complex, were reduced among patients with acquired PAP (n = 4) compared with normal bone marrow donor controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one individual who had complete resolution of lung disease during the period of study, this was temporally associated with correction of this defective in vitro response to GM-CSF and IL-3 on serial assessment. These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease. Based on these observations, we propose a model of the pathogenesis of acquired PAP that suggests the disease arises as a consequence of an acquired clonal disorder within the hematopoietic progenitor cell compartment.     

<Superscript>1</Superscript>H NMR characterization of milk lipids: A comparison between cow and buffalo milk

Characterization of the lipid fraction of raw cow and buffalo milk samples, collected in different breeding areas in Apulia, a region of southern Italy, were performed by means of ¹H NMR. The aim of this work was to establish whether FA composition data obtained by ¹H NMR can be used in the differentiation of buffalo and cow milk samples according to species. A complete assignment of the signals present in the spectrum was attempted by COSY, heteronuclear coherence spectra. Quantification of FA was carried out by inserting the integrals of particular peaks in suitable calculations. Multivariate statistical analysis, conducted on the results of the quantification, permitted buffalo and cow milks to be distinguished.     

Joint Determination of the State Dimension and Autoregressive Order for Models with Markov Regime Switching

Abstract. This paper is concerned with the problem of joint determination of the state dimension and autoregressive order of models with Markov‐switching parameters. A model selection procedure is proposed which is based on optimization of complexity‐penalized likelihood criteria. The efficacy of the procedure is evaluated by means of Monte Carlo experiments.     

A systematic review of the potential hurdles of interoperability to the emergency services in major incidents: recommendations for solutions and alternatives

This study presents a narrative synthesis of a systematic literature review relating to multi-agency interoperability and major incident decision-making in high risk, high stake environments. The review methodology includes the identification of relevant studies, a critical appraisal of the concepts inherent in the main review question and a narrative synthesis of the central themes that relate to the study as a whole. The review firstly outlines what, currently, appear to be the perceived defining features of successful interoperability by using the SAFE-T phase model of major incident decision-making. It then considers whether these defining features are realistically achievable in major incident practice. Findings suggest that the current definition of an interoperable network is too demanding for the inherent complexity and dynamic nature of the major incident task environment. Individual teams tend to focus on agency-specific behaviour, as opposed to coordinated multi-team functioning, and so collective interoperability is not achieved. Inevitably, this reduces the ability to perform collaborative behaviours, including decision-making and action implementation. The paper concludes that aiming for the current conceptualisation of interoperability along a hierarchical command structure may actually inhibit effective decision-making. Instead, multi-agency systems would do better to work towards an improved understanding of a non-hierarchical and decentralised yet interoperable major incident management network. Recommendations include the need to relate theory and practice in the development of multi-agency decision-making via simulation-based training and to deepen our understanding of interoperability to prevent inertia in high risk, high stake major incident environments.     

Coping with uncertainty: police strategies for resilient decision-making and action implementation

This study uses a hostage negotiation setting to demonstrate how a team of strategic police officers can utilize specific coping strategies to minimize uncertainty at different stages of their decision-making in order to foster resilient decision-making to effectively manage a high-risk critical incident. The presented model extends the existing research on coping with uncertainty by (1) applying the RAWFS heuristic (Lipshitz and Strauss in Organ Behav Human Decis Process 69:149–163, 1997) of individual decision-making under uncertainty to a team critical incident decision-making domain; (2) testing the use of various coping strategies during “in situ” team decision-making by using a live simulated hostage negotiation exercise; and (3) including an additional coping strategy (“reflection-in-action”; Schön in The reflective practitioner: how professionals think in action. Temple Smith, London, 1983) that aids naturalistic team decision-making. The data for this study were derived from a videoed strategic command meeting held within a simulated live hostage training event; these video data were coded along three themes: (1) decision phase; (2) uncertainty management strategy; and (3) decision implemented or omitted. Results illustrate that, when assessing dynamic and high-risk situations, teams of police officers cope with uncertainty by relying on “reduction” strategies to seek additional information and iteratively update these assessments using “reflection-in-action” (Schön 1983) based on previous experience. They subsequently progress to a plan formulation phase and use “assumption-based reasoning” techniques in order to mentally simulate their intended courses of action (Klein et al. 2007), and identify a preferred formulated strategy through “weighing the pros and cons” of each option. In the unlikely event that uncertainty persists to the plan execution phase, it is managed by “reduction” in the form of relying on plans and standard operating procedures or by “forestalling” and intentionally deferring the decision while contingency planning for worst-case scenarios.     

A microfluidic optical beam steerer

This paper reports the fabrication and characterization of a prototype microfluidic device that can act as a periodic beam steerer. The prototype is formed by a simple T-junction followed by a serpentine channel that allows generation of a periodical segmented flow of air and water bubbles. If light hits the channel wall with a suitable angle, it can be either transmitted or reflected by the segmented flow, giving rise to an alternating beam steerer. The duty cycle, switching frequency, and overall stability and reproducibility of this prototype system are presented and discussed.