Understanding occipital pressure sores in UK military casualties: a pilot study in healthy military personnel

Introduction The high prevalence of occipital ulcers in UK military casualties observed during the conflict in Afghanistan is a multifactorial phenomenon. However, the consensus is that ulceration is triggered by excessive pressure that is maintained for too long during the use of the general service military stretcher. Thresholds for capillary occlusion are accepted benchmarks to define excessive pressure, but similar thresholds for safe/excessive duration of pressure application do not exist. To address this gap in knowledge, we propose to use the time it takes for a healthy person to feel pain at the back of the head as an initial indication of safe exposure to pressure. Methods Healthy military personnel (16 male/10 female) were asked to lie motionless on a typical general service stretcher until they felt pain. Time-to-pain and the location of pain were recorded. To support the interpretation of results, baseline sensitivity to pain and pressure distribution at the back of the head were also measured. Independent samples t-test was used to assess differences between genders. Results Twenty participants felt pressure-induced soft-tissue pain at the back of the head. The remaining six participants terminated the test due to musculoskeletal pain caused by poor ergonomic positioning. On average, pain at the occiput developed after 31 min (±14 min). Female participants were significantly more sensitive to pain (t(24)=3.038,p=0.006), but time-to-pain did not differ significantly between genders (p>0.05). Conclusions When people lie motionless on a typical military stretcher, the back of the head is the first area of the body that becomes painful due to pressure. The fact that pain develops in ≈30 min can help healthcare providers decide how frequently to reposition their patients who are unable to do this on their own. More research is still needed to directly link time-to-pain with time-to-injury

Overnight information and intraday trading behavior: evidence from NYSE cross-listed stocks and their local market information

Abstract In this paper we study how overnight price movements in local markets affect the trading activity of foreign stocks on the NYSE. We find that local price movements affect not only the opening returns of foreign stocks, but also their returns in the first 30-min interval. The magnitude of local price movements is positively related to price volatility of foreign stocks, and this relation is stronger at the NYSE open and weaker afterward. This result helps explain why intraday price volatility is high at the open and lower at midday. However, local price movements cannot account for intraday variations in trading volume. We also find that trading volume for foreign stocks is strongly correlated with NYSE opening price volatility and weakly correlated with local market overnight price volatility. We interpret the result as evidence that the trading activity of foreign stocks on the NYSE is related more to liquidity trading of US investors and less to local market information

Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands

Genetic testing can diagnose long-QT syndrome (LQTS) in asymptomatic relatives of patients with an identified mutation; however, it is costly and subject to availability. The accuracy of a simple algorithm that incorporates resting and exercise ECG parameters for screening LQTS in asymptomatic relatives was evaluated, with genetic testing as the gold standard. Asymptomatic first-degree relatives of genetically characterized probands were recruited from 5 centers. QT intervals were measured at rest, during exercise, and during recovery. Receiver operating characteristics were used to establish optimal cutoffs. An algorithm for identifying LQTS carriers was developed in a derivation cohort and validated in an independent cohort. The derivation cohort consisted of 69 relatives (28 with LQT1, 20 with LQT2, and 21 noncarriers). Mean age was 35±18 years, and resting corrected QT interval (QTc) was 466±39 ms. Abnormal resting QTc (females ≥480 ms; males ≥470 ms) was 100% specific for gene carrier status, but was observed in only 48% of patients; however, mutations were observed in 68% and 42% of patients with a borderline or normal resting QTc, respectively. Among these patients, 4-minute recovery QTc ≥445 ms correctly restratified 22 of 25 patients as having LQTS and 19 of 21 patients as being noncarriers. The combination of resting and 4-minute recovery QTc in a screening algorithm yielded a sensitivity of 0.94 and specificity of 0.90 for detecting LQTS carriers. When applied to the validation cohort (n=152; 58 with LQT1, 61 with LQT2, and 33 noncarriers; QTc=443±47 ms), sensitivity was 0.92 and specificity was 0.82. A simple algorithm that incorporates resting and exercise-recovery QTc is useful in identifying LQTS in asymptomatic relative

Characterization of the 4D5Flu single-chain antibody with a stimulus-responsive elastin-like peptide linker: A potential reporter of peptide linker conformation

Single-chain antibodies (scFvs) are comprised of IgG variable light and variable heavy domains tethered together by a peptide linker whose length and sequence can affect antigen binding properties. The ability to modulate antigen binding affinity through the use of environmental triggers would be of great interest for many biotechnological applications. We have characterized the antigen binding properties of an anti-fluorescein scFv, 4D5Flu, containing stimulus-responsive short elastin-like peptide linkers and nonresponsive flexible linkers. Comparison of length-matched flexible and short elastin-like peptide linkers indicates that a stimulus-responsive linker can confer stimulus-responsive control of fluorescein binding. A linker length of either six or 10 amino acids proved to have the largest thermally induced response. Similar differences in binding free energy changes indicate a common underlying mechanism of thermal responsiveness. Contrary to the thermal behavior, the effect of salt, another elastin β-turn-inducing stimulus, stabilized antigen binding in the six- and 10-amino-acid linkers such that elastin-like linkers became less stimulus-responsive as compared with flexible linkers. Again, the thermodynamic analysis indicates a common mechanism of salt responsiveness. Characterization of the room-temperature binding affinities and evidence indicating a dimeric state of the scFvs concomitantly suggest the major contribution to the stimulus-responsive behavior derives from the perturbation of interdomain associations, rather than the linker-constrained disruption of the intramolecular association. The ability to use stimulus-responsive peptide modules to exert a novel control over protein function will likely find application in the creation of allosteric antibodies and scFv-based biosensors, and as a platform to enable the evolution of new stimulus-responsive peptides

Randomized Clinical Trial of Thrice-Weekly 4-Month Moxifloxacin or Gatifloxacin Containing Regimens in the Treatment of New Sputum Positive Pulmonary Tuberculosis Patients

<div><p>Background</p><p>Shortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.</p><p>Methods</p><p>Newly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens.</p><p>Results</p><p>Of 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification.</p><p>Conclusions</p><p>4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB.</p><p>Trial Registration</p><p>Clinical Trials Registry of India <a href="http://clinicaltrials.gov/ct2/show/CTRI/2012/10/003060" target="_blank">CTRI/2012/10/003060</a></p></div