Correction of coagulation in the hemophilic dog by transplantation of lymphatic tissue

Available data concerning the non-hepatic source of plasma factor VIII are conflicting. In the present study, dogs with factor VIII deficiency hemophilia were transplanted with spleen or vascularized lymph node grafts obtained from normal donor dogs. Postoperative immunosuppression was done with azathioprine and heterologous antilymphocyte globulin. Four spleen transplants were successful and the recipients had positive technetium sulfide spleen scans along with adequate plasma factor VIII levels for three to eight weeks. Cessation of graft isotope uptake was accompanied by prompt disappearance of plasma factor in all four dogs. Histologically, the grafts were rejected at this time. In one dog, a second spleen graft immediately restored therapeutic factor VIII levels. Four lymph node transplants were successful and plasma factor VIII was detected for one, one, two, and ten weeks. Three dogs rejected their lymph node grafts with disappearance of factor VIII, while one had a viable transplant removed with loss of factor VIII within two days. The data suggest that factor VIII is produced in the lymphatic tissue of the dog. © 1974

Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort

BACKGROUND: Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours. // METHODS: We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials. // RESULTS: Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p < 0.001). // CONCLUSION: SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours. // CLINICAL TRIAL REGISTRATION: NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883

The health outcomes and physical activity in preschoolers (HOPP) study: rationale and design

<p>Abstract</p> <p>Background</p> <p>The early years are the period of growth for which we know the least about the impact of physical activity. In contrast, we know that more than 90 % of school-aged Canadian children, for example, are not meeting physical activity recommendations. Such an activity crisis is a major contributor to recent trends in childhood obesity, to which preschoolers are not immune. The World Health Organization estimated that more than 42 million children under the age of 5 years were overweight world-wide in 2010. If an activity crisis exists during the preschool years, we should also be concerned about its broader impact on health. Unfortunately, the relationship between physical activity and health during the early years is poorly understood. The goal of the Health Outcomes and Physical activity in Preschoolers (HOPP) study is to describe how the prevalence and patterns of physical activity in preschoolers are associated with indices of health.</p> <p>Methods</p> <p>The HOPP study is a prospective cohort study. We aim to recruit 400 3- to 5-year-old children (equal number of boys and girls) and test them once per year for 3 years. Each annual assessment involves 2 laboratory visits and 7 consecutive days of physical activity monitoring with protocols developed in our pilot work. At visit 1, we assess body composition, aerobic fitness, short-term muscle power, motor skills, and have the parents complete a series of questionnaires related to their child’s physical activity, health-related quality of life and general behaviour. Over 7 consecutive days each child wears an accelerometer on his/her waist to objectively monitor physical activity. The accelerometer is programmed to record movement every 3 s, which is needed to accurately capture the intensity of physical activity. At visit 2, we assess vascular structure and function using ultrasound. To assess the associations between physical activity and health outcomes, our primary analysis will involve mixed-effects models for longitudinal analyses.</p> <p>Discussion</p> <p>The HOPP study addresses a significant gap in health research and our findings will hold the potential to shape public health policy for active living during the early years.</p

Synergies, Strengths and Challenges: Findings on Community Capability from a Systematic Health Systems Research Literature Review

Background: Community capability is the combined influence of a community’s social systems and collective resources that can address community problems and broaden community opportunities. We frame it as consisting of three domains that together support community empowerment: what communities have; how communities act; and for whom communities act. We sought to further understand these domains through a secondary analysis of a previous systematic review on community participation in health systems interventions in low and middle income countries (LMICs). Methods: We searched for journal articles published between 2000 and 2012 related to the concepts of “community”, “capability/participation”, “health systems research” and “LMIC.” We identified 64 with rich accounts of community participation involving service delivery and governance in health systems research for thematic analysis following the three domains framing community capability. Results: When considering what communities have, articles reported external linkages as the most frequently gained resource, especially when partnerships resulted in more community power over the intervention. In contrast, financial assets were the least mentioned, despite their importance for sustainability. With how communities act, articles discussed challenges of ensuring inclusive participation and detailed strategies to improve inclusiveness. Very little was reported about strengthening community cohesiveness and collective efficacy despite their importance in community initiatives. When reviewing for whom communities act, the importance of strong local leadership was mentioned frequently, while conflict resolution strategies and skills were rarely discussed. Synergies were found across these elements of community capability, with tangible success in one area leading to positive changes in another. Access to information and opportunities to develop skills were crucial to community participation, critical thinking, problem solving and ownership. Although there are many quantitative scales measuring community capability, health systems research engaged with community participation has rarely made use of these tools or the concepts informing them. Overall, the amount of information related to elements of community capability reported by these articles was low and often of poor quality. Conclusions: Strengthening community capability is critical to ensuring that community participation leads to genuine empowerment. Our simpler framework to define community capability may help researchers better recognize, support and assess it

Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis.

Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear

Vanishing carrier-envelope-phase-sensitive response in optical-field photoemission from plasmonic nanoantennas

At the surfaces of nanostructures, enhanced electric fields can drive optical-field photoemission and thereby generate and control electrical currents at frequencies exceeding 100 THz (refs. 1,2,3,4,5,6,7,8,9,10,11). A hallmark of such optical-field photoemission is the sensitivity of the total emitted current to the carrier-envelope phase (CEP)1,2,3,7,11,12,13,14,15,16,17. Here, we examine CEP-sensitive photoemission from plasmonic gold nanoantennas excited with few-cycle optical pulses. At a critical pulse energy, which we call a vanishing point, we observe a pronounced dip in the magnitude of the CEP-sensitive photocurrent accompanied by a sudden shift of π radians in the photocurrent phase. Analysis shows that this vanishing behaviour arises due to competition between sub-optical-cycle electron emission events from neighbouring optical half-cycles and that both the dip and phase shift are highly sensitive to the precise shape of the driving optical waveform at the surface of the emitter. As the mechanisms underlying the dip and phase shift are a general consequence of nonlinear, field-driven photoemission, they may be used to probe sub-optical-cycle emission processes from solid-state emitters, atoms and molecules. Improved understanding of these CEP-sensitive photocurrent features will be critical to the development of optical-field-driven photocathodes for time-domain metrology and microscopy applications demanding attosecond temporal and nanometre spatial resolution