The pursuit of better atomic clocks has advanced many research areas, providing better quantum state control, new insights in quantum science, tighter limits on fundamental constant variation and ...improved tests of relativity. The record for the best stability and accuracy is currently held by optical lattice clocks. Here we take an important step towards realizing the full potential of a many-particle clock with a state-of-the-art stable laser. Our (87)Sr optical lattice clock now achieves fractional stability of 2.2 × 10(-16) at 1 s. With this improved stability, we perform a new accuracy evaluation of our clock, reducing many systematic uncertainties that limited our previous measurements, such as those in the lattice ac Stark shift, the atoms' thermal environment and the atomic response to room-temperature blackbody radiation. Our combined measurements have reduced the total uncertainty of the JILA Sr clock to 2.1 × 10(-18) in fractional frequency units.
Surgical smoke is omnipresent in the day-to-day life of the surgeon and other medical personnel who work in the operating room. In addition, patients are also exposed, especially and uniquely so in ...laparoscopic cases where smoke is created and trapped in a closed and absorptive space. Surgical smoke has typically been produced by electrocautery but is now ever more present in a new form with the burgeoning use of the laser and the harmonic scalpel. Several cases of transmission of human papillomavirus (HPV) from patient to treating professional via laser smoke have alerted us to the reality that surgical smoke in certain situations is far form benign. However, surgeons rarely take measures to protect themselves, their co-coworkers and patients from surgical smoke. Should we and, if so, how do we differentiate between different types of smoke and should we move toward increasing our efforts to protect ourselves, our co-workers, and patients from it? This article attempts to sort through the available data and draw some reasonable conclusions regarding surgical smoke. In general, surgical smoke is a biohazard and cannot be ignored. At a minimum, surgical smoke is a toxin similar to cigarette smoke. However, other dangers exist. This is especially true in specific circumstances such as when tissue infected with dangerous viruses is aerosolized by lasers. In addition, smoke generated by the harmonic scalpel, being a relatively cold vapor similar to laser smoke, should be further investigated for its potential ill effects and until then, looked upon with reasonable caution. Although not a high-priority in most surgical cases, surgeons should support efforts to minimize OR personnel, patients, and their own exposure to surgical smoke.
Burn injuries are common and often life-threatening trauma. With this trauma comes an interruption of normal hemostasis, with distinct impacts on platelets. Our interest in the relationships between ...burn injury and platelet function stems from two key perspectives: platelet function is a vital component of acute responses to injury, and furthermore the incidence of cardiovascular disease (CVD) is higher in burn survivors compared to the general population. This review explores the impact of burn injury on coagulation, platelet function, and the participation of platelets in immunopathology. Potential avenues of further research are explored, and consideration is given to what therapies may be appropriate for mediating post-burn thrombopathology.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Earlier studies of invasive breast tumors have shown that 60-80% are aneuploid and ≈80% exhibit amplified centrosomes. In this study, we investigated the relationship of centrosome amplification with ...aneuploidy, chromosomal instability, p53 mutation, and loss of differentiation in human breast tumors. Twenty invasive breast tumors and seven normal breast tissues were analyzed by fluorescence in situ hybridization with centromeric probes to chromosomes 3, 7, and 17. We analyzed these tumors for both aneuploidy and unstable karyotypes as determined by chromosomal instability. The results were then tested for correlation with three measures of centrosome amplification: centrosome size, centrosome number, and centrosome microtubule nucleation capacity. Centrosome size and centrosome number both showed a positive, significant, linear correlation with aneuploidy and chromosomal instability. Microtubule nucleation capacity showed no such correlation, but did correlate significantly with loss of tissue differentiation. Centrosome amplification was detected in in situ ductal carcinomas, suggesting that centrosome amplification is an early event in these lesions. Centrosome amplification and chromosomal instability occurred independently of p53 mutation, whereas p53 mutation was associated with a significant increase in centrosome microtubule nucleation capacity. Together, these results demonstrate that independent aspects of centrosome amplification correlate with chromosomal instability and loss of tissue differentiation and may be involved in tumor development and progression. These results further suggest that aspects of centrosome amplification may have clinical diagnostic and/or prognostic value and that the centrosome may be a potential target for cancer therapy.
Self-assembling polycation/DNA complexes represent a promising synthetic vector for gene delivery. However, despite considerable versatility and transfectional activity in vitro, such materials are ...quickly eliminated from the bloodstream following intravenous injection (plasma alpha half-life typically less than 5 min). For targeted systemic delivery a more prolonged plasma circulation of the vector is essential. Here we have examined factors contributing to rapid elimination of poly(L-lysine) (pLL)/DNA complexes from the bloodstream, and implicate the binding of proteins to the polyelectrolyte complexes as a likely cause for their blood clearance. pLL/DNA complexes reisolated from serum associate with several proteins, depending on their net charge, although the major band on SDS-PAGE co-migrates with albumin. Serum albumin binds to pLL/DNA complexes in vitro, forming a ternary pLL/DNA/albumin complex which regains some ethidium bromide fluorescence and fails to move during agarose electrophoresis. Albumin also causes increased turbidity of complexes, and reduces their zeta potential to the same level (-16 mV) as is measured in serum. We propose that rapid plasma elimination of polycation/DNA complexes results from their binding serum albumin and other proteins, perhaps due to aggregation and phagocytic capture or accumulation of the ternary complexes in fine capillary beds.
Background
Current literature indicates that direct‐acting antivirals (DAAs) are cost‐effective to treat compensated cirrhotic patients with hepatitis C. Although already funded by public payers, it ...is unknown whether it is economical to reimburse DAAs within the more advanced decompensated cirrhosis population.
Methods
A state‐transition model was developed to conduct a cost‐utility analysis of sofosbuvir‐velpatasvir (SOF/VEL) plus ribavirin regimen for 12 weeks. The evaluated cohort had a mean age of 58 years and Child‐Turcotte‐Pugh (CTP) class B cirrhosis with decompensated symptoms. A scenario analysis was performed on CTP C patients. We used a payer perspective, a lifetime time horizon and a 1.5% annual discount rate.
Results
While SOF/VEL plus ribavirin treatment for 12 weeks increased costs by $156 676, it provided an extra 4.00 quality‐adjusted life years (QALYs) compared to best supportive care (no DAA therapy). With an incremental cost‐effectiveness ratio of $39 169 per QALY, SOF/VEL plus ribavirin was determined to be cost‐effective at a willingness to pay of $50 000 per QALY. SOF/VEL reduced liver‐related deaths and reduced progression to CTP C cirrhosis by 20.4% and 21.9%, respectively. On the contrary, SOF/VEL regimen resulted in increases in liver transplants and hepatocellular carcinoma (HCC) by 54.0% and 42.5%, respectively. Similar results were found for CTP C patients.
Conclusion
This analysis informs payers that SOF/VEL should continue to be reimbursed in decompensated hepatitis C patients. It also supports the recommendations by the American Association for the Study of Liver Diseases to continue screening for HCC in decompensated cirrhotic patients who have achieved sustained virologic response.
Background
Understanding the relationships between physical fitness characteristics and sports injury may assist with the development of injury minimisation programs. The purpose of this systematic ...review was to investigate the association between physical fitness attributes and sports injury in female, team ball sport players.
Methods
Four scientific databases (MEDLINE, EMBASE, SPORTDiscus, Scopus) and reference lists of relevant research were searched for eligible studies up to September 2, 2019. Full-text articles examining the relationship between physical fitness and sports injury in female, team ball sport players were included. A modified Downs and Black checklist was used to assess methodological quality. Data synthesis determined summary conclusions based on the number of significant relationships divided by the total relationships investigated and reported as a percentage. Level of certainty was identified for summary conclusions based on level of evidence. Sub-analyses regarding competition level, age, and single injury types were also conducted.
Results
A total of 44 studies were included. Data synthesis revealed no associations (low to moderate certainty) between body composition (1/9; 11%), flexibility (18–20%), and balance (2/8; 25%) and ‘any injury’ classification. No associations (mostly of moderate certainty) were found between flexibility (0–27%), muscular strength (0–27%), and body composition (14–33%) and various body region injury classifications, whereas mixed summary conclusions were shown for balance (0-48%). Many associations between physical fitness and sports injury were deemed ‘unknown’ or with an insufficient level of certainty. Sub-analyses revealed no association between strength and noncontact ACL injuries (0/5; 0%) or ankle sprains (0/12; 0%), and between flexibility and ankle sprains (1/5; 20%); however, insufficient certainty of these results exists. Clear associations were concluded between balance and lower body injuries in female, non-elite (10/16; 63%) and junior (9/12; 75%) team ball sport players, with moderate and insufficient certainty of these results, respectively.
Conclusion
Limited evidence is available to demonstrate relationships between physical fitness and sports injury in female, team ball sport players. High-quality evidence investigating the multifactorial nature of sports injury, including the interactions physical fitness qualities have with other injury determinants, is needed to better understand the role of physical fitness in minimising sports injuries in female, team ball sport players.
Trial Registration
CRD42017077374
(PROSPERO on September 14, 2017).
To determine the effects of continuation versus discontinuation of alendronate on BMD and markers of bone turnover, we conducted an extension trial in which 1099 older women who received alendronate ...in the FIT were re‐randomized to alendronate or placebo. Compared with women who stopped alendronate, those continuing alendronate for 3 years maintained a higher BMD and greater reduction of bone turnover, showing benefit of continued treatment. However, among women who discontinued alendronate and took placebo in the extension, BMD remained higher, and reduction in bone turnover was greater than values at FIT baseline, showing persistence of alendronate's effects on bone.
Introduction: Prior trials including the Fracture Intervention Trial (FIT) have found that therapy with alendronate increases BMD and decreases fracture risk for up to 4 years in postmenopausal women with low BMD. However, it is uncertain whether further therapy with alendronate results in preservation or further gains in BMD and if skeletal effects of alendronate continue after treatment is stopped.
Materials and Methods: We conducted a follow‐up placebo‐controlled extension trial to FIT (FIT long‐term extension FLEX) in which 1099 women 60‐86 years of age who were assigned to alendronate in FIT with an average duration of use of 5 years were re‐randomized for an additional 5 years to alendronate or placebo. The results of a preplanned interim analysis at 3 years are reported herein. Participants were re‐randomized to alendronate 10 mg/day (30%), alendronate 5 mg/day (30%), or placebo (40%). All participants were encouraged to take a calcium (500 mg/day) and vitamin D (250 IU/day) supplement. The primary outcome was change in total hip BMD. Secondary endpoints included change in lumbar spine BMD and change in markers of bone turnover (bone‐specific alkaline phosphatase and urinary type I collagen cross‐linked N‐telopeptide).
Results: Among the women who had prior alendronate therapy in FIT, further therapy with alendronate (5 and 10 mg groups combined) for 3 years compared with placebo maintained BMD at the hip (2.0% difference; 95% CI, 1.6‐2.5%) and further increased BMD at the spine (2.5% difference; 95% CI, 1.9‐3. 1%). Markers of bone turnover increased among women discontinuing alendronate, whereas they remained stable in women continuing alendronate. Cumulative increases in BMD at the hip and spine and reductions in bone turnover from 8.6 years earlier at FIT baseline were greater for women continuing alendronate compared with those discontinuing alendronate. However, among women discontinuing alendronate and taking placebo in the extension, BMD remained higher and reduction in bone turnover was greater than values at FIT baseline.
Conclusions: Compared with women who stopped alendronate after an average of 5 years, those continuing alendronate maintained a higher BMD and greater reduction of bone turnover, showing benefit of continued alendronate treatment on BMD and bone turnover. On discontinuation of alendronate therapy, rates of change in BMD at the hip and spine resumed at the background rate, but discontinuation did not result in either accelerated bone loss or a marked increase in bone turnover, showing persistence of alendronate's effects on bone. Data on the effect of continuation versus discontinuation on fracture risk are needed before making definitive recommendations regarding the optimal length of alendronate treatment.
This study sought to assess the effect of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers on all-cause mortality in patients with left ventricular (LV) systolic dysfunction according ...to gender, race, and the presence of diabetes.
Major randomized clinical trials have established that ACE inhibitors and beta-blockers have life-saving benefits in patients with LV systolic dysfunction. Most patients enrolled in these trials were Caucasian men. Whether an equal effect is achieved in women, non-Caucasians, and patients with major comorbidities has not been established.
The authors performed a meta-analysis of published and individual patient data from the 12 largest randomized clinical trials of ACE inhibitors and beta-blockers to produce random effects estimates of mortality for subgroups.
Data support beneficial reductions in all-cause mortality for the use of beta-blockers in men and women, the use of ACE inhibitors and some beta-blockers in black and white patients, and the use of ACE inhibitors and beta-blockers in patients with or without diabetes. Women with symptomatic LV systolic dysfunction probably benefit from ACE inhibitors, but women with asymptomatic LV systolic dysfunction may not have reduced mortality when treated with ACE inhibitors (pooled relative risk = 0.96; 95% confidence interval: 0.75 to 1.22). The pooled estimate of three beta-blocker studies supports a beneficial effect in black patients with heart failure, but one study assessing bucindolol reported a nonsignificant increase in mortality.
Angiotensin-converting enzyme inhibitors and beta-blockers provide life-saving benefits in most of the subpopulations assessed. Women with asymptomatic LV systolic dysfunction may not achieve a mortality benefit when treated with ACE inhibitors.
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