Synthesis of Polyproline Spacers between NIR Dye Pairs for FRET to Enhance Photoacoustic Imaging

With the goal of enhancing the emission of ultra-sound (US) waves in photoacoustic imaging (PAI) for the detection of cancer we discovered an effective system for Förster Resonance Energy Transfer (FRET) composed of a near infrared fluorescent (NIRF) dye and a NIR quencher (NIRQ) dye separated by a polyproline peptide spacer. In PAI, a newly developed imaging technique, the signal is generated by excitation of cells using pulsed infrared lasers and measurement of resulting US waves using detectors. NIRF dyes can increase the sensitivity of PAI signal, particularly when used in targeted molecular imaging agents (TMIAs). However, most of the energy of absorption is likely lost during fluorescence. Our hypothesis was that if the fluorescence could be quenched by FRET, all of the energy from the laser could be converted to a substantially stronger US signal from the NIR dyes. In FRET, an optimized distance between the NIRF and NIRQ dyes is essential, but has not yet been determined for this dual dye system. To determine the appropriate distance, we designed and synthesized a polyproline spacer as a rigid “molecular ruler”. Multiple polyproline spacers (di, tetra, octa) were synthesized and coupled first to two NIRF dyes, Cy5.5 and IR770TI, using a modular synthetic approach developed by our group. When the emission resulting from FRET between NIRF dye pairs was evaluated, a strong FRET effect was observed from the octaproline dye pair, with twice the signal as the tetraproline. Furthermore, it was found that the FRET effect could be influenced by the solvents due to the dye aggregation. The polyproline approach was then applied to the synthesis and evaluation of NIRF-NIRQ dye pairs resulting in the discovery that tetra and octaproline NIRF-NIRQ systems yield nearly complete FRET quenching. The new FRET system is a valuable tool for future research in PAI to provide a higher, more sensitive signal. Samples have been submitted to collaborators for evaluation using PAI instrumentation at nearby cancer research centers

Structure, Stability and Superconductivity of N-doped Lutetium Hydrides at kbar Pressures

The structure of the material responsible for the room temperature and near ambient pressure superconductivity reported in an N-doped lutetium hydride [Nature, 615, 244 (2023)] has not been conclusively determined. Herein, density functional theory calculations are performed in an attempt to uncover what it might be. Guided by a range of strategies including crystal structure prediction and modifications of existing structure types, we present an array of Lu-N-H phases that are dynamically stable at experimentally relevant pressures. Although none of the structures found are thermodynamically stable, and none are expected to remain superconducting above 17 K at 10 kbar, a number of metallic compounds with fcc Lu lattices -- as suggested by the experimental X-ray diffraction measurements of the majority phase -- are identified. The system whose calculated equation of states matches best with that measured for the majority phase is fluorite-type LuH2, whose 10 kbar superconducting critical temperature was estimated to be 0.09 K using the Allen-Dynes modified McMillan equation.Comment: 11 pages, 8 figure

A perspective on implementation outcomes and strategies to promote the uptake of COVID-19 vaccines

Recent articles have highlighted the importance of incorporating implementation science concepts into pandemic-related research. However, limited research has been documented to date regarding implementation outcomes that may be unique to COVID-19 vaccinations and how to utilize implementation strategies to address vaccine program-related implementation challenges. To address these gaps, we formed a global COVID-19 implementation workgroup of implementation scientists who met weekly for over a year to review the available literature and learn about ongoing research during the pandemic. We developed a hierarchy to prioritize the applicability of lessons learned from the vaccination-related implementation literature. We identified applications of existing implementation outcomes as well as identified additional implementation outcomes. We also mapped implementation strategies to those outcomes. Our efforts provide rationale for the utility of using implementation outcomes in pandemic-related research. Furthermore, we identified three additional implementation outcomes: availability, health equity, and scale-up. Results include a list of COVID-19 relevant implementation strategies mapped to the implementation outcomes

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Structural Diversity and Superconductivity in S-P-H Ternary Hydrides Under Pressure

Evolutionary structure searches revealed a plethora of stable and low-enthalpy metastable phases in the S-P-H ternary phase diagram under pressure. A wide variety of crystalline structure types were uncovered ranging from those possessing one-dimensional chains, two-dimensional sheets based on S-H or S-P-H square lattices as well as S-H or P-H honeycombs, and cage-like structures. Some of the cage-like structures could be derived from doping the high-pressure high-temperature superconducting $Im\bar{3}m$ H$_3$S phase with phosphorous. Most of the discovered compounds were metallic, however those derived from $Im\bar{3}m$ H$_3$S lattices with low levels of P-doping were predicted to possess the highest superconducting critical temperatures ($T_c$s). The propensity for phosphorous to assume octahedral coordination, as well as the similar radii of sulfur and phosphorous are key to maintaining a high density of states at the Fermi level in $Im\bar{3}m$ S$_{0.875}$P$_{0.125}$H$_3$, whose $T_c$ was estimated to be similar to that of H$_3$S at 200~GPa

A First-Principles Exploration of NaxSy Binary Phases at 1 atm and Under Pressure

Interest in Na-S compounds stems from their use in battery materials at 1 atm, as well as the potential for superconductivity under pressure. Evolutionary structure searches coupled with Density Functional Theory calculations were employed to predict stable and low-lying metastable phases of sodium poor and sodium rich sulfides at 1 atm and within 100–200 GPa. At ambient pressures, four new stable or metastable phases with unbranched sulfur motifs were predicted: Na2S3 with C 2 / c and Imm2 symmetry, C 2 -Na2S5 and C 2 -Na2S8. Van der Waals interactions were shown to affect the energy ordering of various polymorphs. At high pressure, several novel phases that contained a wide variety of zero-, one-, and two-dimensional sulfur motifs were predicted, and their electronic structures and bonding were analyzed. At 200 GPa, P 4 / m m m -Na2S8 was predicted to become superconducting below 15.5 K, which is close to results previously obtained for the β -Po phase of elemental sulfur. The structures of the most stable M3S and M4S, M = Na, phases differed from those previously reported for compounds with M = H, Li, K

Superconductivity in Dilute Hydrides of Ammonia under Pressure

The past decade has witnessed great progress in predicting and synthesizing polyhydrides that exhibit superconductivity under pressure. Dopants allow these compounds to become metals at pressures lower than those required to metallize elemental hydrogen. Here, we show that by combining the fundamental planetary building blocks of molecular hydrogen and ammonia, conventional superconducting compounds can be formed at high pressure. Through extensive theoretical calculations, we predict metallic metastable structures with NHn (n = 10, 11, 24) stoichiometries that are based on NH4+ superalkali cations and complex hydrogenic lattices. The hydrogen atoms in the molecular cation contribute to the superconducting mechanism, and the estimated superconducting critical temperatures, Tc's, are comparable to the highest values computed for the alkali metal polyhydrides. The largest calculated (isotropic Eliashberg) Tc is ∼180 K for Pnma-NH10 at 300 GPa. Our results suggest that other molecular cations can be mixed with hydrogen under pressure, yielding superconducting compounds