One of the key challenges in developing quantum networks is to generate single photons with high brightness, purity, and long temporal coherence. Semiconductor quantum dots potentially satisfy these ...requirements; however, due to imperfections in the surrounding material, the coherence generally degrades with increasing excitation power yielding a broader emission spectrum. Here we overcome this power-broadening regime and demonstrate an enhanced coherence at exciton saturation where the detected count rates are highest. We detect single-photon count rates of 460 000 counts per second under pulsed laser excitation while maintaining a single-photon purity greater than 99%. Importantly, the enhanced coherence is attained with quantum dots in ultraclean wurtzite InP nanowires, where the surrounding charge traps are filled by exciting above the wurtzite InP nanowire band gap. By raising the excitation intensity, the number of possible charge configurations in the quantum dot environment is reduced, resulting in a narrower emission spectrum. Via Monte Carlo simulations we explain the observed narrowing of the emission spectrum with increasing power. Cooling down the sample to 300 mK, we further enhance the single-photon coherence twofold as compared to operation at 4.5 K, resulting in a homogeneous coherence time, T2, of 1.2 ns, and two-photon interference visibility as high as 83% under strong temporal postselection (~5% without temporal postselection).
Pulmonary rehabilitation (PR) improves exercise tolerance in COPD patients. Tiotropium is a once-daily, inhaled anticholinergic bronchodilator that provides sustained 24-h improvements in airflow and ...lung hyperinflation reduction. We hypothesized that ventilatory mechanics improvements from tiotropium would permit enhanced ability to train muscles of ambulation and therefore augment exercise tolerance benefits of PR
In a randomized, double-blind, placebo-controlled trial (tiotropium, n = 47; placebo, n = 44), tiotropium (18 μg qd) was administered to COPD patients participating in 8 weeks of PR (treadmill training three times a week; ≥ 30 min per session) at 17 sites. Study drug was administered 5 weeks prior to, 8 weeks during, and 12 weeks following PR. The primary end point was treadmill walking (0% incline) endurance time at 80% of maximum speed attained in an initial incremental test. The transition dyspnea index (TDI), St. George's respiratory questionnaire (SGRQ), and rescue albuterol use were secondary end points
Mean age of the 93 participants was 67 years, 57% were men, and mean FEV1 was 0.88 L (34% predicted)
Mean endurance time differences (tiotropium minus placebo) prior to PR, at the end of PR, and 12 weeks after PR were 1.65 min (p = 0.183), 5.35 min (p = 0.025), and 6.60 min (p = 0.018), respectively. Mean TDI focal scores at the end of PR were 1.75 for tiotropium and 0.91 for placebo (p > 0.05). At 12 weeks after PR, TDI focal scores were 1.75 for tiotropium and 0.08 for placebo (p < 0.05). Relative to placebo, tiotropium improved SGRQ total scores by 3.86 at the end of PR and 4.44 at 12 weeks after PR (p > 0.05). Mean albuterol use declined following PR plus tiotropium, compared to PR alone (p ≤ 0.05 for 17 of 25 weeks)
Tiotropium in combination with PR improved endurance of a constant work rate treadmill task and produced clinically meaningful improvements in dyspnea and health status compared to PR alone. Improvements with tiotropium were sustained for 3 months following PR completion
The core public health measures of handwashing, wearing face masks (recently reclassified as "barrier face coverings," or BFCs),1 and avoiding crowding through physical distancing proved their value ...as we awaited the development and global distribution of COVID-19 vaccines.2-4 These practices demanded significant attention in the professional community as well as by the public regarding their utility, optimal practice, and duration to foster public health in various, evolving scenarios.The COVID-19 pandemic represented a crisis for both the professionals who strived to give guidance and the public who tried to interpret its value relative to social and economic sacrifices. More specifically, what have the months of pandemic taught us for the future as we slowly try to make the world safer? Physical distancing, initially termed social distancing, will slowly return to a quasinormal level. Hand hygiene vigilance will hopefully not atrophy, but rather become an elevated norm. Face masks, a daily part of our lives throughout the current pandemic, can be relegated to the wastebasket.
The drug development process of demonstrating an agent is safe, effective and pure has, with rare exception, proven an exemplary path in translational research. The basic science, the clinical trials ...and the chemistry, manufacturing and control have served public health well. This carefully regulated approach forms the basis of a drug label with data from these studies also used to convey risk and benefit to prescribing physicians through the channels of medical literature and drug promotion by the industry. The latter is also important to public health in that such promotion must be based in the approved indication, be truthful, not be misleading and be substantiated by sufficient evidence. Why then is the emergence of “medical marijuana” any different? While substantial evidence exists for some conditions and some related products have undergone careful investigation through to NDA approval, most claims are not substantiated by research but driven by misguided enthusiasm. While recreational use of marijuana is not at debate here, nor is the right of an individual patient to explore cannabis therapeutically; however, allowing broad unsubstantiated claims around medicinal cannabis to infiltrate the general public is a disservice. To distill the potential medical benefits through the pharmacologic understanding of the endocannabinoid system, cannabis should follow the traditional drug development process or one that improves upon it. Until then, claims should remain as stated hypothesis to accept or reject.
Recent infectious outbreaks preceding the COVID-19 crisis resulted in the evolution of vigilance for preparedness against the next pandemic. This vigilance was maintained to varying degrees in ...different jurisdictions.
To evaluate the evolution of vigilance following previous epidemics and pandemics and the subsequent atrophy of vigilance prior to the COVID-19 global pandemic.
We evaluated documentation discussing US, Canada, and South Korea from March 2002 to October 2021. Our policy search strategy was rooted in academic literature, government documents and media reports.
In the US, there were examples of atrophy of vigilance; however, there was clear understanding of pandemic readiness actions that were simply not executed amongst political chaos. In Canada, political mishaps were less evident at the time the pandemic unfolded. Nevertheless, atrophy was evident with erosion in preparedness programs following SARS. South Korea appeared least subjected to atrophy of vigilance. The more recent MERS outbreak prompted evolution of sustained vigilance and compliance with basic public health measures such as mask wearing.
Policy options need to be explored and instituted that increase protection of preparedness programs through institutional safeguards and accountability measure.
Tiotropium, a once-daily anticholinergic, and salmeterol represent two inhaled, long-acting bronchodilators from different pharmacologic classes. A trial was designed to examine the efficacy and ...safety of both compounds with multiple outcome measures, including lung function, dyspnea, and health-related quality of life (HRQoL) in patients with COPD.
A 6-month, randomized, placebo-controlled, double-blind, double-dummy, parallel-group study of tiotropium, 18 μg once daily via dry-powder inhaler, compared with salmeterol, 50 μg bid via metered-dose inhaler, was conducted in patients with COPD. Efficacy was assessed by 12-h monitoring of spirometry, transition dyspnea index (TDI), and the St. George's Respiratory Questionnaire (SGRQ).
A total of 623 patients participated (tiotropium, n= 209; salmeterol, n = 213; and placebo, n = 201). The groups were similar in age (mean, 65 years), gender (75% men), and baseline FEV1 (mean, 1.08 ± 0.37 L; percent predicted, 40 ± 12% ± SD). Compared with placebo treatment, the mean predose morning FEV1 following 6 months of therapy increased significantly more for the tiotropium group (0.14 L) than the salmeterol group (0.09 L; p < 0.01). The average FEV1 (0 to 12 h) for tiotropium was statistically superior to salmeterol (difference, 0.08 L; p < 0.001). Tiotropium improved TDI focal score by 1.02 U compared with placebo (p = 0.01), whereas there was no significant change in TDI focal score with salmeterol (0.24 U). Tiotropium was superior to salmeterol in improving TDI focal score (p < 0.05). At 6 months, the mean improvement in SGRQ total score vs baseline was tiotropium, − 5.14 U (p < 0.05 vs placebo); salmeterol, − 3.54 U (p = 0.4 vs placebo); and placebo, − 2.43 U. A statistically higher proportion of patients receiving tiotropium achieved at least a 4-U change in SGRQ score compared to patients receiving placebo. Both active drugs reduced the need for rescue albuterol (p < 0.0001).
Tiotropium once daily produces superior bronchodilation, improvements in dyspnea, and proportion of patients achieving meaningful changes in HRQoL compared to twice-daily salmeterol in patients with COPD.
The Emergency Use Authorization (EUA) originated in 2004 because of the need for emergency medical countermeasures (MCMs) against potential bioterrorist attacks. The EUA also proved useful in dealing ...with subsequent pandemics and has emerged as a critical regulatory pathway for therapeutics and vaccines throughout the Coronavirus Disease 2019 (COVID-19) pandemic. With the EUA process in the USA, we witnessed emergency authorizations, their expansions, as well as withdrawal of previously authorized products, which exemplifies the dynamic nature of scientific review of EUA products. EUAs proved vital for the first group of COVID-19 vaccines, including the temporary pause of one vaccine while emergency safety issues were evaluated. Although this review on the EUA is primarily focused on the USA, distinctions were made with other jurisdictions such as Europe and Canada with respect to the emergency authorizations of the vaccines. Finally, we discuss some important differences following EUA and formal new drug/vaccine application (NDA/BLA) approvals.
Dyspnoea is a primary symptom of chronic obstructive pulmonary disease (COPD). The baseline (BDI) and transition (TDI) dyspnoea indices are commonly used instruments to assess breathlessness and the ...impact of intervention. Its validity and pattern of response in multinational clinical trials has not been established. In a retrospective analysis of a cohort of 997 COPD patients who received tiotropium, salmeterol or placebo, in addition to usual care, the validity and pattern of response of the BDI and TDI were examined. The BDI was significantly correlated with the dyspnoea diary (DD) score and the symptom and activity components of the St. George's respiratory questionnaire (SGRQ), establishing concurrent validity. Furthermore, the TDI was also correlated with the changes in DD, SGRQ symptom and activity scores. Construct validity was established by the association between baseline forced expiratory volume in one second (FEV1) and BDI and AFEVI with TDI. Physician's global evaluation (PGE) was significantly associated with BDI as well as APGE with TDI. Significant correlations have also been observed when the cohorts were classified according to native English and native non-English speaking countries. A change in PGE of 1 category (i.e. 2 units on an 8-point scale) was associated with a mean TDI of approximately 1 unit (0.9-1.3 mean focal score), lending further support to the clinical significance of this change inherent in the instrument's descriptors. TDI responders (i.e. focal score < or = 1 unit) used less supplemental salbutamol, had fewer exacerbations and had significantly improved health status as measured by impacts and total SGRQ scores compared with nonresponders. In conclusion, the transition dyspnoea index is a valid instrument when used in a multinational clinical trial and the patterns of response confirm a 1-unit change in the transition dyspnoea index focal score as being clinically important.
In this study, the proton dynamics of hydrogen bonds for two forms of crystalline aspirin was investigated by the Born–Oppenheimer molecular dynamics (BOMD) method. Analysis of the geometrical ...parameters of hydrogen bonds using BOMD reveals significant differences in hydrogen bonding between the two crystalline forms of aspirin, Form I and Form II. Analysis of the trajectory for Form I shows spontaneous proton transfer in cyclic dimers, which is absent in Form II. Quantization of the O–H stretching modes allows a detailed discussion on the strength of hydrogen-bonding interactions. The focal point of our study is examination of the hydrogen bond characteristics in the crystal structure and clarification of the influence of hydrogen bonding on the presence of the two crystalline forms of aspirin. In the BOMD method, thermal motions were taken into account. Solving the Schrödinger equation for the snapshots of 2D proton potentials, extracted from MD, gives the best agreement with IR spectra. The character of medium-strong hydrogen bonds in Form I of aspirin was compared with that of weaker hydrogen bonds in aspirin Form II. Two proton minima are present in the potential function for the hydrogen bonds in Form I. The band contours, calculated by using one- and two-dimensional O–H quantization, reflect the differences in the hydrogen bond strengths between the two crystalline forms of aspirin, as well as the strong hydrogen bonding in the cyclic dimers of Form I and the medium-strong hydrogen bonding in Form II.
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