The excavation of Non Ban Jak, Northeast Thailand - A report on the first three seasons

Non Ban Jak is a large, moated site located in the upper Mun Valley, Northeast Thailand. Excavations over three seasons in 2011-4 have revealed a sequence of occupation that covers the final stage of the local Iron Age. The site is enclosed by two broad moats and banks, and comprises an eastern and a western mound separated by a lower intervening area. The first season opened an 8 by 8 m square on the eastern mound, while the second and third seasons uncovered part of the low terrain rising into the western mound, encompassing an area of 25 by 10 m. The former revealed a sequence of industrial, residential and mortuary activity that involved the construction of houses, kiln firing of ceramic vessels and the interment of the dead within residences. The latter involved four phases of a late Iron Age cemetery, which again incorporated house floors and wall foundations, as well as further evidence for ceramic manufacture. The excavation sheds light on a late Iron Age town occupied at the threshold of state formation

So far, yet so close: α-Catenin dimers help migrating cells get together

Epithelial cells in tissues use their actin cytoskeletons to stick together, whereas unattached cells make active plasma membrane protrusions to migrate. In this issue, Wood et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612006) show that the junction component α-catenin is critical in freely moving cells to promote adhesion and migration

The cAMP-producing agonist beraprost inhibits human vascular smooth muscle cell migration via exchange protein directly activated by cAMP

This work was supported by the British Heart foundation (grant FS/11/23/28730). J.S.M. was funded by a British Heart Foundation PhD studentship. Funding to pay the Open Access publication charges for this article was provided by the Charities Open Access Fund (UK).Peer reviewedPublisher PD

HCO3- transport through anoctamin/transmembrane protein ANO1/TMEM16A, in pancreatic acinar cells, regulates luminal pH

The identification of ANO1/TMEM16A as the likely calcium-dependent chloride channel of exocrine glands has led to a more detailed understanding of its biophysical properties. This includes a calcium-dependent change in channel selectivity and evidence that HCO3-permeability can be significant. Here we use freshly isolated pancreatic acini that preserve the luminal structure to measure intraluminal pH and test the idea that ANO1/TMEM16A contributes to luminal pH balance. Our data show that, under physiologically relevant stimulation with 10 pm cholesystokinin, the luminal acid load that results from the exocytic fusion of zymogen granules is significantly blunted by HCO3-buffer in comparison with HEPES, and that this is blocked by the specific TMEM16A inhibitor T16inh-A01. Furthermore, in a model of acute pancreatitis, we observed substantive luminal acidification and provide evidence that ANO1/TMEM16A acts to attenuate this pH shift. We conclude that ANO1/TMEM16A is a significant pathway in pancreatic acinar cells for HCO3-secretion into the lumen

Speech and language therapy for aphasia following stroke

Background  Aphasia is an acquired language impairment following brain damage that affects some or all language modalities: expression and understanding of speech, reading, and writing. Approximately one third of people who have a stroke experience aphasia.  Objectives  To assess the effects of speech and language therapy (SLT) for aphasia following stroke.  Search methods  We searched the Cochrane Stroke Group Trials Register (last searched 9 September 2015), CENTRAL (2015, Issue 5) and other Cochrane Library Databases (CDSR, DARE, HTA, to 22 September 2015), MEDLINE (1946 to September 2015), EMBASE (1980 to September 2015), CINAHL (1982 to September 2015), AMED (1985 to September 2015), LLBA (1973 to September 2015), and SpeechBITE (2008 to September 2015). We also searched major trials registers for ongoing trials including ClinicalTrials.gov (to 21 September 2015), the Stroke Trials Registry (to 21 September 2015), Current Controlled Trials (to 22 September 2015), and WHO ICTRP (to 22 September 2015). In an effort to identify further published, unpublished, and ongoing trials we also handsearched theInternational Journal of Language and Communication Disorders(1969 to 2005) and reference lists of relevant articles, and we contacted academic institutions and other researchers. There were no language restrictions.  Selection criteria  Randomised controlled trials (RCTs) comparing SLT (a formal intervention that aims to improve language and communication abilities, activity and participation) versus no SLT; social support or stimulation (an intervention that provides social support and communication stimulation but does not include targeted therapeutic interventions); or another SLT intervention (differing in duration, intensity, frequency, intervention methodology or theoretical approach).  Data collection and analysis  We independently extracted the data and assessed the quality of included trials. We sought missing data from investigators.  Main results  We included 57 RCTs (74 randomised comparisons) involving 3002 participants in this review (some appearing in more than one comparison). Twenty-seven randomised comparisons (1620 participants) assessed SLT versus no SLT; SLT resulted in clinically and statistically significant benefits to patients' functional communication (standardised mean difference (SMD) 0.28, 95% confidence interval (CI) 0.06 to 0.49, P = 0.01), reading, writing, and expressive language, but (based on smaller numbers) benefits were not evident at follow-up. Nine randomised comparisons (447 participants) assessed SLT with social support and stimulation; meta-analyses found no evidence of a difference in functional communication, but more participants withdrew from social support interventions than SLT. Thirty-eight randomised comparisons (1242 participants) assessed two approaches to SLT. Functional communication was significantly better in people with aphasia that received therapy at a high intensity, high dose, or over a long duration compared to those that received therapy at a lower intensity, lower dose, or over a shorter period of time. The benefits of a high intensity or a high dose of SLT were confounded by a significantly higher dropout rate in these intervention groups. Generally, trials randomised small numbers of participants across a range of characteristics (age, time since stroke, and severity profiles), interventions, and outcomes.  Authors' conclusions  Our review provides evidence of the effectiveness of SLT for people with aphasia following stroke in terms of improved functional communication, reading, writing, and expressive language compared with no therapy. There is some indication that therapy at high intensity, high dose or over a longer period may be beneficial. HIgh-intensity and high dose interventions may not be acceptable to all

Phosphoinositide 3-kinase p110δ promotes lumen formation through the enhancement of apico-basal polarity and basal membrane organization

Signalling triggered by adhesion to the extracellular matrix plays a key role in the spatial orientation of epithelial polarity and formation of lumens in glandular tissues. Phosphoinositide 3-kinase signalling in particular is known to influence the polarization process during epithelial cell morphogenesis. Here, using Madin–Darby canine kidney epithelial cells grown in 3D culture, we show that the p110d isoform of phosphoinositide 3-kinase co-localizes with focal adhesion proteins at the basal surface of polarized cells. Pharmacological, siRNA- or kinase-dead-mediated inhibition of p110d impair the early stages of lumen formation, resulting in inverted polarized cysts, with no laminin or type IV collagen assembly at cell/extracellular matrix contacts. p110d also regulates the organization of focal adhesions and membrane localization of dystroglycan. Thus, we uncover a previously unrecognized role for p110d in epithelial cells in the orientation of the apico-basal axis and lumen formation

A qualitative study of decision-making and safety in ambulance service transitions

Background Decisions made by front-line ambulance staff are often time critical and based on limited information, but wrong decisions in this context could have serious consequences for patients. There has been little research carried out in the ambulance service setting to identify areas of risk associated with decisions about patient care. Aim The aim of this study was to qualitatively examine potential system-wide influences on decision-making in the ambulance service setting and to identify useful areas for future research and intervention. Methods We used a multisite, multimethod qualitative approach across three ambulance service trusts. In phase 1 we carried out 16 interviews to contextualise the study and provide discussion points for phase 2. For phase 2, university and ambulance service researchers observed paramedics on 34 shifts and 10 paramedics completed ‘digital diaries’ that reported challenges to decision-making or to patient safety. Six focus groups were held, three with staff (n = 21) and three with service users (n = 23). From observation and diary data we developed a typology of decisions made at the scene. Data from these and other sources were also coded within a human factors framework and then thematically analysed to identify influences on those decisions. In phase 3, workshops were held at each site to allow participants and stakeholders (n = 45) to comment on the study findings. Participants were asked to rank influences on decisions using a ‘paired comparison’ method. Results Interviews provided the context for further qualitative exploration. Nine types of decision were identified from observations and digital diaries, ranging from emergency department conveyance and specialist emergency pathways to non-conveyance. A synthesis of findings from the observations, diaries and staff focus groups revealed seven overarching system influences on decision-making and potential risk factors: meeting increasing demand for emergency care; impacts of performance regime and priorities on service delivery; access to appropriate care options; disproportionate risk aversion; education, training and professional development for crews; communication and feedback to crews; and ambulance service resources. Safety culture issues were also identified. Data from the service user focus groups reflected similar issues to those identified from the staff focus groups. Service user concerns included call handling and communication, triage, patient involvement in decisions, balancing demand, resources, access to care, risk aversion, geographical location and vulnerable patients. Group discussions highlighted a lack of awareness by the public of how best to use emergency and urgent care services. Workshop attendees were satisfied that the findings reflected relevant issues. The two issues ranked highest for warranting attention were staff training and development and access to alternative care. Conclusions Multiple qualitative methods allowed a range of perspectives to be accessed and validation of issues across perspectives. Recommendations for future research include exploring effective ways of providing access to alternative care pathways to accident and emergency, assessing public awareness and expectations of ambulance and related services, exploring safe ways of improving telephone triage decisions and assessing the effects of different staff skill levels on patient safety

Bypassing nearest hospital for more distant neuroscience care in head-injured adults with suspected traumatic brain injury: findings of the head injury transportation straight to neurosurgery (HITS-NS) pilot cluster randomised trial

OBJECTIVE: Reconfiguration of trauma services, with direct transport of patients with traumatic brain injury (TBI) to specialist neuroscience centres (SNCs)-bypassing non-specialist acute hospitals (NSAHs), could improve outcomes. However, delays in stabilisation of airway, breathing and circulation (ABC) may worsen outcomes when compared with selective secondary transfer from nearest NSAH to SNC. We conducted a pilot cluster randomised controlled trial to determine the feasibility and plausibility of bypassing suspected patients with TBI -directly into SNCs-producing a measurable effect. SETTING: Two English Ambulance Services. PARTICIPANTS: 74 clusters (ambulance stations) were randomised within pairs after matching for important characteristics. Clusters enrolled head-injured adults-injured nearest to an NSAH-with internationally accepted TBI risk factors and stable ABC. We excluded participants attended by Helicopter Emergency Medical Services or who were injured more than 1 hour by road from nearest SNC. INTERVENTIONS: Intervention cluster participants were transported directly to an SNC bypassing nearest NSAH; control cluster participants were transported to nearest NSAH with selective secondary transfer to SNC. OUTCOMES: Trial recruitment rate (target n=700 per annum) and percentage with TBI on CT scan (target 80%) were the primary feasibility outcomes. 30-day mortality, 6-month Extended Glasgow Outcome Scale and quality of life were secondary outcomes. RESULTS: 56 ambulance station clusters recruited 293 patients in 12 months. The trial arms were similar in terms of age, conscious level and injury severity. Less than 25% of recruited patients had TBI on CT (n=70) with 7% (n=20) requiring neurosurgery. Complete case analysis showed similar 30-day mortality in the two trial arms (control=8.8 (2.7-14.0)% vs intervention=9.4(2.3-14.0)%). CONCLUSION: Bypassing patients with suspected TBI to SNCs gives an overtriage (false positive) ratio of 13:1 for neurosurgical intervention and 4:1 for TBI. A measurable effect from a full trial of early neuroscience care following bypass is therefore unlikely. TRIAL REGISTRATION NUMBER: ISRCTN68087745

Graduate Recital:David Shewan, French Horn

Kemp Recital Hall Sunday Evening April 6, 2008 9:00p.m