GENERATION OF CYTOTOXIC T LYMPHOCYTES IN VITRO : III. Velocity Sedimentation Studies of the Differentiation and Fate of Effector Cells in Long-Term Mixed Leukocyte Cultures

Separation of cells by velocity sedimentation at unit gravity was utilized to investigate the physical properties of cytotoxic thymus-derived lymphocytes (CTL) generated in long-term mixed leukocyte cultures (MLC). In kinetic studies, CTL were found almost exclusively in the large cell fractions at the peak of the response on day 4, whereas the majority of CTL in day 14 MLC had the sedimentation properties of small lymphocytes. Reculture until day 14 of cells fractionated on the basis of size on day 4 indicated that the small CTL were derived exclusively from cells which had been large on day 4. Re-exposure of day 14 MLC cells to the original stimulating alloantigens resulted in significant cell proliferation and rapid regeneration of CTL activity. Cell fractionation experiments demonstrated that the cells in the day 14 MLC population which responded to the secondary allogeneic stimulus were small T lymphocytes, and that these cells rapidly developed into large, highly cytotoxic CTL following stimulation. Moreover, by restimulating on day 14 fractions which were selected on the basis of size on day 4, it was found that the responding small lymphocytes were themselves the progeny of cells which were large at the peak of the response. Since CTL and CTL progenitors showed concomitant changes in physical properties with time, the possibility exists that they belong to the same cell lineage, and hence that CTL can differentiate into cells which are no longer cytotoxic, but capable of mounting an anamnestic response

A historic jet-emission minimum reveals hidden spectral features in 3C 273

Aims. The aim of this work is to identify and study spectral features in the quasar 3C 273 usually blended by its strong jet emission. Method. A historic minimum in the sub-millimetre emission of 3C 273 triggered coordinated multi-wavelength observations in June 2004. X-ray observations from the INTEGRAL, XMM-Newton and RXTE satellites are complemented by ground-based optical, infrared, millimetre and radio observations. The overall spectrum is used to model the infrared and X-ray spectral components. Results. Three thermal dust emission components are identified in the infrared. The dust emission on scales from 1 pc to several kpc is comparable to that of other quasars, as expected by AGN unification schemes. The observed weakness of the X-ray emission supports the hypothesis of a synchrotron self-Compton origin for the jet component. There is a clear soft-excess and we find evidence for a very broad iron line which could be emitted in a disk around a Kerr black hole. Other signatures of a Seyfert-like X-ray component are not detected.Comment: 4 pages. Accepted for publication in A&A Letter

Variability of Quasars at 10 microns

Twenty five low redshift quasars have been monitored for several decades at five near- and mid-infrared wavelengths to detect rapid variations which would indicate that a nonthermal component was present in the "10 micron bump". Such variability has apparently been detected in several radio loud quasars and in the radio quiet quasar PG1535+547. In addition, the structure function of PG1226+023 shows that an apparently periodic component is present in its near-infrared emission.Comment: AAS LaTex, 33 figures in 2 postscript files, AJ, accepte

Assessing wellbeing at school entry using the strengths and difficulties questionnaire: professional perspectives

<p>Background: Emotional and behavioural disorders in early childhood are related to poorer academic attainment and school engagement, and difficulties already evident at the point of starting school can affect a child’s later social and academic development. Successful transfer from pre-school settings to primary education is helped by communication between pre-school staff and primary school teachers. Typically, in Scotland, pre-school establishments prepare individual profiles of children before they start school around the age of five years, highlighting their strengths and development needs, for transfer to primary schools. There is, however, no consistent approach to the identification of potential social, emotional and behavioural problems. In 2010, in one local authority area in Scotland, the Strengths and Difficulties Questionnaire (SDQ) was introduced for children about to start school as a routine, structured, component of the transition process to help teachers plan support arrangements for classes and individual children. The SDQ assesses emotional, conduct, hyperactivity/ inattention and peer-relationship problems as well as pro-social behaviour. In order to be an effective means of communicating social and emotional functioning, the use of instruments such as the SDQ needs to be practicable. Finding out the views of pre-school education staff with experience of assessing children using the SDQ was, therefore, essential to establish its future utility.</p> <p>Aim: The purpose of this study was to explore the views of pre-school education staff about assessing social and emotional wellbeing of children at school entry using the SDQ. The objectives were to examine the opinions of pre-school workers about completing the SDQ and to elicit their thoughts on the value of doing this and their perceptions of the usefulness of the information collected.</p> <p>Method: Pre-school establishments were approached using a purposive sampling strategy in order to achieve a mix of local authority (n=14) and ‘partnership’ establishments (n=8) as well as different socio-economic areas. Semi-structured interviews (n=25) were conducted with pre-school head teachers (n=14) and child development officers (n=11) in order to explore the process of completing the SDQ along with perceptions of its value. The interviews were transcribed verbatim and analysed thematically.</p> <p>Results: In general, staff in pre-school establishments viewed the use of the SDQ positively. It was seen as a chance to highlight the social and emotional development of children rather than just their academic or educational ability. Most felt that the SDQ had not identified anything they did not already know about a child. A minority, nevertheless, suggested that a previously unrecognised potential difficulty was brought to light, most commonly emotional problems. Completing the SDQ was felt to be relatively straightforward even though the staff felt under pressure from competing priorities. Concerns were, however, raised about the potential of labelling a child at an early stage of formal education.</p> <p>Conclusion: The findings from this small scale study suggest that, from the point of view of pre-school education staff, it is feasible to assess children systematically for social and behavioural problems as part of the routine transition process at school entry.</p&gt

Caesarean Section among Referred and Self-Referred Birthing Women: A Cohort Study from a Tertiary Hospital, Northeastern Tanzania.

The inequity in emergency obstetric care access in Tanzania is unsatisfactory. Despite an existing national obstetric referral system, many birthing women bypass referring facilities and go directly to higher-level care centres. We wanted to compare Caesarean section (CS) rates among women formally referred to a tertiary care centre versus self-referred women, and to assess the effect of referral status on adverse outcomes after CS. We used data from 21,011 deliveries, drawn from the birth registry of a tertiary hospital in northeastern Tanzania, during 2000-07. Referral status was categorized as self-referred if the woman had bypassed or not accessed referral, or formally-referred if referred by a health worker. Because CS indications were insufficiently registered, we applied the Ten-Group Classification System to determine the CS rate by obstetric group and referral status. Associations between referral status and adverse outcomes after CS delivery were analysed using multiple regression models. Outcome measures were CS, maternal death, obstetric haemorrhage ≥ 750 mL, postpartum stay > 9 days, neonatal death, Apgar score < 7 at 5 min and neonatal ward transfer. Referral status contributed substantially to the CS rate, which was 55.0% in formally-referred and 26.9% in self-referred birthing women. In both groups, term nulliparous singleton cephalic pregnancies and women with previous scar(s) constituted two thirds of CS deliveries. Low Apgar score (adjusted OR 1.42, 95% CI 1.09-1.86) and neonatal ward transfer (adjusted OR 1.18, 95% CI 1.04-1.35) were significantly associated with formal referral. Early neonatal death rates after CS were 1.6% in babies of formally-referred versus 1.2% in babies of self-referred birthing women, a non-significant difference after adjusting for confounding factors (adjusted OR 1.37, 95% CI 0.87-2.16). Absolute neonatal death rates were > 2% after CS in breech, multiple gestation and preterm deliveries in both referral groups. Women referred for delivery had higher CS rates and poorer neonatal outcomes, suggesting that the formal referral system successfully identifies high-risk birth, although low volume suggests underutilization. High absolute rates of post-CS adverse outcomes among breech, multiple gestation and preterm deliveries suggest the need to target self-referred birthing women for earlier professional intrapartum care

Neonatal tolerance to Mls-1a determinants: deletion or anergy of Vβ6 + T lymphocytes depending upon MHC compatibility of neonatally injected cells

Recent investigations in mice revealed that natural immunologlcal tolerance to endogenous minor lymphocyte-stimulating locus 1a (MIs-1a antigen correlates primarily with deletion of Mls-1aspeciflc Vβ6+ T lymphocytes In the thymus. Similar mechanisms account for acquired tolerance in some Instancessince the neonatal injection of Mls-1 a-expressing MHC compatible cells in neonatal mice within the first 24 hof life causes clonal deletion of Vβ6+ T cells. Here we demonstrate that Vβ6+ T cells are not deleted In mice neonatally treated with Mls-1a spleen cells expressing allogenelc H-2 molecules. However, when such non-deleted Vβ6+ T cells were tested In vitro, no interleukin 2 (IL-2) secretion or proliferation was observed after Mls-1a stimulation. This non-responsive state could be overcome by addition of exogenous IL-2, consistent with the fact that Vβ6+ cells enlarged and expressed IL-2 receptors upon Mls-1a stimulation. Furthermore, the same neonatally treated mice showed In vitro functional unresponsiveness of cytotoxic T cells but not of IL-2-secreting cells specific for the tolerated allogeneic MHC antigens. Taken together, our data Indicate that neonatal tolerance to Mls-1a can be accomplished by either clonal deletion or clonal anergy, and that it does not necessarily correlate with tolerance to MHC determinant

Preventing strokes in people with atrial fibrillation by improving ABC.

Nationally, anticoagulation for atrial fibrillation (AF) is improving but remains characterised by marked provider variation. Uncontrolled blood pressure and coronary artery disease further increase cardiovascular risk. Redbridge Clinical Commissioning Group (CCG) and local National Health Service (NHS) hospital trusts supported a programme to improve anticoagulation, blood pressure and cholesterol management; the ABC of AF improvement. The programme was delivered by a clinical pharmacist in 43 general practices, who used Active Patient Link (APL-AF) software to identify and electronically review the records of AF patients potentially suitable for anticoagulation. These patients were invited for a general practitioner (GP)-pharmacist consultation with initiation of anticoagulation where appropriate. Blood pressure and lipid treatment were also optimised. The university-based Clinical Effectiveness Group (CEG) provided software support using standard data entry templates from which the APL-AF software was enabled. This identified suitable patients (eg, on aspirin monotherapy, no treatment or inappropriate dual treatments) for clinical and treatment review. It also reported real-time overall practice performance. Additionally, GP education on direct oral anticoagulant initiation in general practices, use of software and performance reviews, took place for all practices in Redbridge. A weekly multidisciplinary team (MDT) video conference discussed complex patients with a cardiologist, haematologist, GP with specialist interest in cardiology, GP coordinator and clinical pharmacist. This enabled sharing of patient records between GPs and hospital specialists with improved communication and learning. Over 1 year 2016-2017, anticoagulation in eligible AF patients (CHA2DS2-VASc≥2) increased significantly by 6.3% from 77.0% to 83.3% (p<0.0001), in comparison to 2.8% average improvement in England. Exception reporting was also significantly reduced from 10.0% to 5.8%; a reduction of 4.2% in comparison to a reduction in England of 1.5%. Use of antiplatelet monotherapy was approximately halved, from 12.3% to 6.4%. These methods are being scaled locally in other London CCGs and are potentially scalable nationally, specifically targeting the poorer performing CCGs

Adenosine Metabolized From Extracellular ATP Ameliorates Organ Injury by Triggering A2BR Signaling

BACKGROUND: Trauma and a subsequent hemorrhagic shock (T/HS) result in insufficient oxygen delivery to tissues and multiple organ failure. Extracellular adenosine, which is a product of the extracellular degradation of adenosine 5\u27 triphosphate (ATP) by the membrane-embedded enzymes CD39 and CD73, is organ protective, as it participates in signaling pathways, which promote cell survival and suppress inflammation through adenosine receptors including the A METHODS: T/HS shock was induced by blood withdrawal from the femoral artery in wild-type, global knockout (CD39, CD73, A RESULTS: T/HS upregulated the expression of CD39, CD73, and the A CONCLUSION: In conclusion, the CD39-CD73-