Severity of delayed (“secondary”) cerebral energy failure after acute hypoxia-ischemia is related to the time integral of acute ATP depletion

The aim of this study was to reproduce the delayed (secondary) cerebral energy failure previously described in birth-asphyxiated newborn infants and to investigate relationships between primary insult severity and the extent of the delayed energy failure. Phosphorus (³¹P) magnetic resonance spectroscopy (MRS) at 7 T was used to study the brains of 12 newborn piglets during an acute, reversible, cerebral hypoxic-ischemic episode which continued until nucleotide triphosphates (NTP) were depleted. After reperfusion and reoxygenation, spectroscopy was continued for 48 h. High-energy metabolite concentrations returned to near normal levels after the insult, but later they fell as delayed energy failure developed. The time integral of NTP depletion in the primary insult correlated strongly with the minimum [phosphocreatine (PCr)]/[inorganic orthophosphate (P_i)] observed 24–48 h after the insult. (Linear regression analysis gave slope –8.04 h^–1; ordinate intercept=1.23;r=0.92;P<0.0001.) This model is currently being used to investigate the therapeutic potential of various cerebroprotective strategies including hypothermia.     

Relationships between subjective and objective assessments of stress at slaughter and meat quality in pigs

A study was carried out to relate subjective and objective measures of stress at slaughter and meat quality in pigs. Thirteen slaughter plants were visited. The systems used for handling the pigs pre-slaughter and the levels of stress experienced by the animals were subjectively assessed. The sound level immediately before stunning was also measured. Generally, systems that were rated as being most stressful also produced higher levels of sound, probably because of the vocalisations of the pigs. As the size of plant increased, there was a tendency for the level of stress, and the recorded sound level, to increase. This appeared to be because larger plants operated faster and were more likely to use restraining conveyors supplied by races to handle the animals before stunning. The restraint associated with these seems stressful to pigs. Five plants were selected for further study. Two had been assessed as having handling systems that produced a low level of stress in the pigs, one as having a system producing a medium level, and two as having poor systems producing high levels of stress. Blood samples were collected at exsanguination, and meat quality was assessed. As the level of subjectively assessed stress experienced by the pigs increased, so did the average blood levels of lactate and creatine phosphokinase (CPK). There was also a progressive increase in the potential incidence of pale, soft, exudative (PSE) and dark, firm, dry (DFD) meat in the plants using more stressful handling systems. Additionally, there were positive relationships between sound level and lactate and CPK, and sound level and indices of poorer meat quality. Cortisol concentrations were not different in pigs killed in the different systems and probably reflect events earlier in the handling process, such as in transport and lairage, rather than the stress experienced immediately before stunning. The overall conclusion was that subjective assessments of the stress suffered by pigs correlate well with objective measures and that higher stress levels are associated with poorer meat quality.     

Entrepreneurial acquisitions,open innovation and UK high growth SMEs

This paper examines the dynamics of entrepreneurial acquisitions undertaken by UK high growth small and medium enterprises (SMEs). While entrepreneurial acquisitions are increasingly deployed by SMEs, little is known about their antecedents, motivational drivers and organisational outcomes. Drawing on detailed case study evidence from Scotland, the key factor found to be driving these acquisitions was the desire to augment and exploit technological complementarities between the acquiring and acquired firms. Acquisition can therefore be conceptualised as an advanced stage of the outside-in ‘open innovation’ strategies proactively used within these innovative SMEs. Firms executing this strategy typically have an acute propensity for risk, a desire for close customer engagement, effective business models and strong external orientation. The work suggests that greater attention should be paid within M&A theory to the dynamics of these types of smaller scale entrepreneurial acquisitions.     

Surface integrity of Inconel 718 by hybrid selective laser melting and milling

ABSTRACT

While selective laser melting (SLM) offers design freedom of metal parts with much less material consumption, there exist several limitations, including high surface roughness, low-dimensional accuracy, and high tensile residual stresses. To make functional parts with high form accuracy and superior surface integrity, an as-SLM part needs finishing to remove the deposited surface material. The integration of machining and SLM creates a hybrid manufacturing route to overcome the inherited limitations of SLM. However, little study has been done to characterise surface integrity of an as-SLM part followed by machining (e.g. hybrid SLM-milling). In this paper, surface, integrity including surface roughness, microstructure, and microhardness, have been characterised for IN718 samples processed by the hybrid process. It has been found that microhardness varies with the scan direction and the use of coolant in the subsequent milling, and surface integrity can be significantly improved by the hybrid SLM-milling route.     

Creutzfeldt-Jakob disease in a husband and wife

A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 1.5-year clinical course. Four and a half years later, his then 55-year-old widow died from CJD after a 1-month illness. Both patients had typical clinical and neuropathologic features of the disease, and pathognomonic proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in both brains. Neither patient had a family history of neurologic disease, and molecular genetic analysis of their PrP genes was normal. No medical, surgical, or dietary antecedent of CJD was identified; therefore, we are left with the unanswerable alternatives of human-to-human transmission or the chance occurrence of sporadic CJD in a husband and wife.     

Isolation and characterization of a monoclonal anti-quadruplex DNA antibody from autoimmune "viable motheaten" mice

A cell line that produces an autoantibody specific for DNA quadruplex structures has been isolated and cloned from a hybridoma library derived from 3-month-old nonimmunized autoimmune, immunodeficient "viable motheaten" mice. This antibody has been tested extensively in vitro and found to bind specifically to DNA quadruplex structures formed by two biologically relevant sequence motifs. Scatchard and nonlinear regression analyses using both one- and two-site models were used to derive association constants for the antibody-DNA binding reactions. In both cases, quadruplexes had higher association constants than triplex and duplex molecules. The anti-quadruplex antibody binds to the quadruplex formed by the promoter-region-derived oligonucleotide d(CGCG4GCG) (Ka = 3.3 x 10(6) M-1), and has enhanced affinity for telomere-derived quadruplexes formed by the oligonucleotides d(TG4) and d(T2G4T2G4T2G4T2G4) (Ka = 5.38 x 10(6) and 1.66 x 10(7) M-1, respectively). The antibody binds both types of quadruplexes but has preferential affinity for the parallel four-stranded structure. In vitro radioimmunofilter binding experiments demonstrated that purified anti-DNA quadruplex antibodies from anti-quadruplex antibody-producing tissue culture supernatants have at least 10-fold higher affinity for quadruplexes than for triplex and duplex DNA structures of similar base composition and length. The antibody binds intramolecular DNA triplexes formed by d(G4T3G4T3C4) and d(C4T3G4T3G4), and the duplex d(CGCGCGCGCG)2 with an affinities of 6. 76 x 10(5), 5.59 x 10(5), and 8.26 x 10(5) M-1, respectively. Competition experiments showed that melted quadruplexes are not effective competitors for antibody binding when compared to native structures, confirming that the quadruplex is bound structure-specifically. To our knowledge, this is the first immunological reagent known to specifically recognize quadruplex structures. Subsequent sequence analysis demonstrates homologies between the antibody complementarity determining regions and sequences from Myb family telomere binding proteins, which are hypothesized to control cell aging via telomeric DNA interactions. The presence of this antibody in the autoimmune repertoire suggests a possible linkage between autoimmunity, telomeric DNA binding proteins, and aging.     

Communicating do-not-resuscitate orders with a computer-based system

BACKGROUND: Do-not-resuscitate (DNR) orders for critically ill patients are frequently miscommunicated between attending physicians, house staff, and nurses. A computer-based system was developed to improve the communication of a procedure-specific DNR order form. METHODS: Concordance of understanding of patients' DNR status was measured with the use of unstructured DNR orders (period 1), procedure-specific DNR order forms (period 2), and procedure-specific DNR order forms administered with a computer-based communication system (period 3). The 3 components of the DNR order assessed were (1) the clinical events to which the DNR order applied, (2) whether the DNR order withheld all elements of cardiopulmonary resuscitation, and (3) whether other treatments were to be withheld. RESULTS: For the 147 patients, the computer-based system in period 3 (n = 71) improved concordance for attending physicians and nurses or residents for all 3 of the DNR components compared with period 1 (n = 40) and some of the DNR components compared with period 2 (n = 36). Concordance was "substantial" or "almost perfect" as measured by the K statistic during period 3. The proportion of agreement for the composite of all 3 components of the DNR order increased during each period (P<.001, period 3 vs period 1). Overall agreement between all caregivers for the composite DNR order also improved from period 1 (22.2%) to period 2 (47.8%) and period 3 (61.9%; P<.001 vs period 1). Errors in order entry were detected by physicians because of the computer system and corrected in 9.9% of DNR orders in period 3. Progress note documentation of DNR status did not improve during period 3. The procedures of period 3 were considered acceptable by the physician and nursing staff. CONCLUSION: A computer-based system combined with a procedure-specific DNR order form improves communication of patients' DNR status in a critical care setting.     

Why talk about mental states? The significance of children's conversations with friends, siblings, and mothers

Natural language data from 38 47-month-olds recorded at home in unstructured observations were analyzed and comparisons made of characteristics of mental state term use in child-friend, child-sibling, and child-mother dyads. Significantly more references to mental states were made by the children in conversations with siblings and friends than with mothers. Frequent use of mental state terms by both partners was related to cooperative interaction in both child-friend and child-sibling dyads and several associations were found with measures of language fluency, gender, and maternal education, although these varied across the 2 dyads. Children's use of mental state terms in conversations with siblings and friends was correlated with their performance on two false belief measures. Results highlight the importance of extending investigations into the social implications of the development of children's "theories of mind."