Enhanced Vascularization of Cultured Skin Substitutes Genetically Modified to Overexpress Vascular Endothelial Growth Factor11The authors declared in writing to have no conflict of interest.

Cultured skin substitutes have been used as adjunctive therapies in the treatment of burns and chronic wounds, but they are limited by lack of a vascular plexus. This deficiency leads to greater time for vascularization compared with native skin autografts and contributes to graft failure. Genetic modification of cultured skin substitutes to enhance vascularization could hypothetically lead to improved wound healing. To address this hypothesis, human keratinocytes were genetically modified by transduction with a replication incompetent retrovirus to overexpress vascular endothelial growth factor, a specific and potent mitogen for endothelial cells. Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates inoculated with human fibroblasts and either vascular endothelial growth factor-modified or control keratinocytes were prepared, and were cultured in vitro for 21 d. Northern blot analysis demonstrated enhanced expression of vascular endothelial growth factor mRNA in genetically modified keratinocytes and in cultured skin substitutes prepared with modified cells. Furthermore, the vascular endothelial growth factor-modified cultured skin substitutes secreted greatly elevated levels of vascular endothelial growth factor protein throughout the entire culture period. The bioactivity of vascular endothelial growth factor protein secreted by the genetically modified cultured skin substitutes was demonstrated using a microvascular endothelial cell growth assay. Vascular endothelial growth factor-modified and control cultured skin substitutes were grafted to full-thickness wounds on athymic mice, and elevated vascular endothelial growth factor mRNA expression was detected in the modified grafts for at least 2 wk after surgery. Vascular endothelial growth factor-modified grafts exhibited increased numbers of dermal blood vessels and decreased time to vascularization compared with controls. These results indicate that genetic modification of keratinocytes in cultured skin substitutes can lead to increased vascular endothelial growth factor expression, which could prospectively improve vascularization of cultured skin substitutes for wound healing applications

Optical absorption of ion-beam sputtered amorphous silicon coatings

Low mechanical loss at low temperatures and a high index of refraction should make silicon optimally suited for thermal noise reduction in highly reflective mirror coatings for gravitational wave detectors. However, due to high optical absorption, amorphous silicon (aSi) is unsuitable for being used as a direct high-index coating material to replace tantala. A possible solution is a multimaterial design, which enables exploitation of the excellent mechanical properties of aSi in the lower coating layers. The possible number of aSi layers increases with absorption reduction. In this work, the optimum heat treatment temperature of aSi deposited via ion-beam sputtering was investigated and found to be 450 °C. For this temperature, the absorption after deposition of a single layer of aSi at 1064 nm and 1550 nm was reduced by more than 80%

Experimental results for nulling the effective thermal expansion coefficient of fused silica fibres under a static stress

We have experimentally demonstrated that the effective thermal expansion coefficient of a fused silica fibre can be nulled by placing the fibre under a particular level of stress. Our technique involves heating the fibre and measuring how the fibre length changes with temperature as the stress on the fibre was systematically varied. This nulling of the effective thermal expansion coefficient should allow for the complete elimination of thermoelastic noise and is essential for allowing second generation gravitational wave detectors to reach their target sensitivity. To our knowledge this is the first time that the cancelation of the thermal expansion coefficient with stress has been experimentally observed

Utility of Two iPhone Device Apps in Assessing Heart Rate at Rest and During Activity

Heart rate (HR) is a critical physiological variable used for prescribing exercise, assessing fitness level and tracking fitness improvements. Electrocardiography (ECG) stands as the criterion measure of HR. While recent development of HR-detecting mobile device applications (apps) has made evaluating HR more convenient; their degree of accuracy is unknown. Therefore, the purpose of this current study was to examine the accuracy and reliability of two-iPhone applications to detect HR at rest and during low-intensity exercise conditions. Eighteen female and 22 male subjects (26 + 9.5 yrs) were prepped for simultaneous detection of HR via three methods: ECG and two HR-detecting apps. App 1, a camera-based app called Azumio Instant Heart Rate (CAM), was used by placement of a finger over the camera lens of the mobile device. App 2, a microphone-based app called Heart Monitor by Bluespark, was employed via placement of an external microphone over the radial pulse. The participants underwent a series of 5-minute stages: seated rest followed by cycle then treadmill walking at low intensities. HR was recorded concurrently, at several time intervals from the three methods once a steady-state HR was reached. The means of the three devices were compared via ANOVA with the significance level set, a priori, at 0.05. Correlation analysis was employed to investigate relationships between the apps and ECG. No statistical difference was found between the CAM and ECG HR (p \u3e 0.05) during the resting and cycle stages. However, during the treadmill phase, there was a significant difference (p = 0.018) between CAM and ECG. Nevertheless, there was a significant (p \u3c 0.05), positive correlation between CAM and ECG under the resting, cycle and treadmill conditions (r = .966, r = .984, r = .877, respectively). Significant differences (p \u3c 0.05) were found for each condition when comparing ECG and MIC HR. Data also revealed poor correlations (p \u3e 0.05; r between -.004 and -.136) between MIC and ECG. The utility of CAM and MIC-based apps to detect HR remains in question as evidence appears to indicate exercise mode and app specificity. Caution should be shown when using these devices. The CAM-based app may accurately detect HR during resting and seated cycling but not during treadmill activity. The MIC-based app is not recommended for use in any condition. Of note, statistical significance may not mitigate usefulness when considering the accuracy of palpation. Additional research is necessary

Benign Conduction Abnormalities in Response to Acute, Moderately-High, Simulated Altitude Exposure

Acclimatization to altitude can improve endurance performance above levels achieved solely by training at sea level. There is natural limitation in the applicability of employing terrestrial altitude training – namely proximity. A simple, non-cumbersome method of simulating altitude is desirable to many types of endurance athletes. The Alto2Lab (Pharma Pacific Inc.), consisting of primarily a breathing tube and silo stack, has shown some potential in this role. There is a lack of evidence regarding whether simulated altitude exposure triggers abnormal cardiovascular responses. The aim of this study was to provide initial evidence of cardiac changes associated with usage patterns that follow distributor guidelines. Twenty-five participants (mean age 29 ± 10.7; 16 males; 9 females) volunteered for the study. Subjects underwent a baseline ECG recording followed by ECG recording during sham (4-5 mins), hypoxia (~6 mins), and recovery (3-4 mins) phases. The sham phase consisted of subjects breathing normoxive air through a foam-filled silo system. The sham stack mimicked the look and feel of the silo system used to produce hypoxia with the difference being a single, soda lime-filled silo. A recovery phase followed hypoxia. Pulse oximetry (SpO2) was used to assess oxygen saturation. Cochran’s Q was employed to test the frequencies of responses across the phases. An independent, blinded, experienced clinician (DK) analyzed the recordings. Two subjects were removed from the final analysis (inability to finish the protocol, baseline right bundle branch block). All subjects demonstrated an increase in heart rate (mean = +16.8 ± 8.0) during the hypoxia (mean oxygen saturation = 82 ± 4.1%) phase. No ECG ischemic changes were seen across any of the phases. Benign conduction abnormalities (sinus arrhythmia = 9; junctional rhythms = 4) occurred with some regularity during hypoxia. These abnormalities occurred with less frequency during the sham and recovery phases. It is possible that an altered breathing pattern or an inadequate washout period between phases might account for these findings. Overall, there was no significant relationship between the heart response and phase (p = .375). While the Alto2Lab did not produce any ECG changes indicative of an ischemic response, the present study used a small sample of healthy, recreationally-active participants. A larger study employing patients among higher risk categories would provide data that is not currently present in the literature and to which this trial cannot speak

Gaps in detailed knowledge of human papillomavirus (HPV) and the HPV vaccine among medical students in Scotland

<p>Background: A vaccination programme targeted against human papillomavirus (HPV) types16 and 18 was introduced in the UK in 2008, with the aim of decreasing incidence of cervical disease. Vaccine roll out to 12–13 year old girls with a catch-up programme for girls aged up to 17 years and 364 days was accompanied by a very comprehensive public health information (PHI) campaign which described the role of HPV in the development of cervical cancer.</p> <p>Methods: A brief questionnaire, designed to assess acquisition of knowledge of HPV infection and its association to cervical cancer, was administered to two different cohorts of male and female 1st year medical students (school leavers: 83% in age range 17–20) at a UK university. The study was timed so that the first survey in 2008 immediately followed a summer's intensive PHI campaign and very shortly after vaccine roll-out (150 students). The second survey was exactly one year later over which time there was a sustained PHI campaign (213 students).</p> <p>Results: We addressed three research questions: knowledge about three specific details of HPV infection that could be acquired from PHI, whether length of the PHI campaign and/or vaccination of females had any bearing on HPV knowledge, and knowledge differences between men and women regarding HPV. No female student in the 2008 cohort had completed the three-dose vaccine schedule compared to 58.4% of female students in 2009. Overall, participants’ knowledge regarding the sexually transmitted nature of HPV and its association with cervical cancer was high in both year groups. However, in both years, less than 50% of students correctly identified that HPV causes over 90% of cases of cervical cancer. Males gave fewer correct answers for these two details in 2009. In 2008 only around 50% of students recognised that the current vaccine protects against a limited subset of cervical cancer-causing HPV sub-types, although there was a significant increase in correct response among female students in the 2009 cohort compared to the 2008 cohort.</p> <p>onclusions: This study highlights a lack of understanding regarding the extent of protection against cervical cancer conferred by the HPV vaccine, even among an educated population in the UK who could have a vested interest in acquiring such knowledge. The intensive PHI campaign accompanying the first year of HPV vaccination seemed to have little effect on knowledge over time. This is one of the first studies to assess detailed knowledge of HPV in both males and females. There is scope for continued improvements to PHI regarding the link between HPV infection and cervical cancer.</p&gt

E/S0 Galaxies on the Blue Color-Stellar Mass Sequence at z=0: Fading Mergers or Future Spirals?

We identify a population of morphologically defined E/S0 galaxies lying on the blue sequence at the present epoch. Using three samples, we analyze blue-sequence E/S0s with stellar masses >10^8 Msun, arguing that individual objects may be evolving either up toward the red sequence or down into the blue sequence. Blue-sequence E/S0 galaxies become more common with decreasing stellar mass, comprising <2% of E/S0s near the "shutdown mass" M_s ~ 1-2 x 10^11 Msun, increasing to >5% near the "bimodality mass" M_b ~ 3 x 10^10 Msun, and sharply rising to >20-30% below the "threshold mass" M_t ~ 4-6 x 10^9 Msun. The strong emergence of blue-sequence E/S0s below M_t coincides with a previously reported global increase in mean atomic gas fractions below M_t for galaxies of all types on both sequences, suggesting that the availability of cold gas may be basic to blue-sequence E/S0s' existence. Environmental analysis reveals that many sub-M_b blue-sequence E/S0s reside in low to intermediate density environments. In mass-radius and mass-sigma scaling relations, blue-sequence E/S0s are more similar to red-sequence E/S0s than to late-type galaxies, but they represent a transitional class. While some of them, especially in the high-mass range from M_b to M_s, resemble major-merger remnants that will likely fade onto the red sequence, most blue-sequence E/S0s below M_b show signs of disk and/or pseudobulge building, which may be enhanced by companion interactions. We argue that sub-M_b blue-sequence E/S0s occupy a "sweet spot" in stellar mass and concentration, with both abundant gas and optimally efficient star formation, which may enable the formation of large spiral disks. [abridged]Comment: AJ, submitted, revised, 21 pages with 15 figures (one in two parts, one color); full resolution version available at http://www.physics.unc.edu/~sheila/kgb.pd

Trial of early, goal-directed resuscitation for septic shock.

BACKGROUND: Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. METHODS: We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. RESULTS: We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. CONCLUSIONS: In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.)

Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock.

BACKGROUND: Early goal-directed therapy (EGDT) is recommended in international guidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness. OBJECTIVES: The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 year; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness. DESIGN: A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. SETTING: Fifty-six NHS hospitals in England. PARTICIPANTS: A total of 1260 patients who presented at EDs with septic shock. INTERVENTIONS: EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1. MAIN OUTCOME MEASURES: All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year. RESULTS: Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the analysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died [p = 0.90; absolute risk reduction -0.3%, 95% confidence interval (CI) -5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20]. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced cardiovascular support days in critical care for the EGDT group. At 1 year, the incremental net benefit for EGDT versus usual resuscitation was negative at -£725 (95% CI -£3000 to £1550). The probability that EGDT was more cost-effective than usual resuscitation was below 30%. There were no significant differences in any other secondary outcomes, including health-related quality of life, or adverse events. LIMITATIONS: Recruitment was lower at weekends and out of hours. The intervention could not be blinded. CONCLUSIONS: There was no significant difference in all-cause mortality at 90 days for EGDT compared with usual resuscitation among adults identified with early septic shock presenting to EDs in England. On average, costs were higher in the EGDT group than in the usual-resuscitation group while quality-adjusted life-years were similar in both groups; the probability that it is cost-effective is < 30%. FUTURE WORK: The ProMISe (Protocolised Management In Sepsis) trial completes the planned trio of evaluations of EGDT across the USA, Australasia and England; all have indicated that EGDT is not superior to usual resuscitation. Recognising that each of the three individual, large trials has limited power for evaluating potentially important subgroups, the harmonised approach adopted provides the opportunity to conduct an individual patient data meta-analysis, enhancing both knowledge and generalisability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36307479. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 97. See the NIHR Journals Library website for further project information

A patient safety toolkit for family practices

Objectives: Major gaps remain in our understanding of primary care patient safety. We describe a toolkit for measuring patient safety in family practices. Methods: Six tools were used in 46 practices. These tools were: NHS Education for Scotland Trigger Tool, NHS Education for Scotland Medicines Reconciliation Tool, Primary Care Safequest, Prescribing Safety Indicators, PREOS-PC, and Concise Safe Systems Checklist. Results: PC-Safequest showed that most practices had a well-developed safety climate. However, the Trigger Tool revealed that a quarter of events identified were associated with moderate or substantial harm, with a third originating in primary care and avoidable. Although medicines reconciliation was undertaken within 2 days in >70% of cases, necessary discussions with a patient/carer did not always occur. The prescribing safety indicators identified 1,435 instances of potentially hazardous prescribing or lack of recommended monitoring (from 92,649 patients). The Concise Safe Systems Checklist found that 25% of staff thought their practice provided inadequate follow-up for vulnerable patients discharged from hospital and inadequate monitoring of non-collection of prescriptions. Most patients had a positive perception of the safety of their practice although 45% identified at least one safety problem in the past year. Conclusions: Patient safety is complex and multidimensional. The Patient Safety Toolkit is easy to use and hosted on a single platform with a collection of tools generating practical and actionable information. It enables family practices to identify safety deficits that they can review and change procedures to improve their patient safety across a key sets of patient safety issues