Return to the Pre-Injury Level of Sport after Anterior Cruciate Ligament Reconstruction: A Practical Review with Medical Recommendations.

Returning to sport after anterior cruciate ligament reconstruction (ACLR) can be a challenging and complex process for the athlete, with the rate of return to the pre-injury level of sport observed to be less than athlete expectations. Of the athletes that do return to sport (RTS), knee re-injury rates remain high, and multiple studies have observed impaired athletic performance upon RTS after ACLR as well as reduced playing time, productivity, and career lengths. To mitigate re-injury and improve RTS outcomes, multiple RTS after ACLR consensus statements/clinical practice guidelines have recommended objective RTS testing criteria to be met prior to medical clearance for unrestricted sports participation. While the achievement of RTS testing criteria can improve RTS rates after ACLR, current criteria do not appear valid for predicting safe RTS. Therefore, there is a need to review the various factors related to the successful return to the pre-injury level of sport after ACLR, clarify the utility of objective performance testing and RTS criteria, further discuss safe RTS decision-making as well as present strategies to reduce the risk of ACL injury/re-injury upon RTS. This article provides a practical review of the current RTS after ACLR literature, as well as makes medical recommendations for rehabilitation and RTS decision-making after ACLR.

Trap-integrated fluorescence detection with silicon photomultipliers for sympathetic laser cooling in a cryogenic Penning trap.

We present a fluorescence-detection system for laser-cooled 9Be+ ions based on silicon photomultipliers (SiPMs) operated at 4 K and integrated into our cryogenic 1.9 T multi-Penning-trap system. Our approach enables fluorescence detection in a hermetically sealed cryogenic Penning-trap chamber with limited optical access, where state-of-the-art detection using a telescope and photomultipliers at room temperature would be extremely difficult. We characterize the properties of the SiPM in a cryocooler at 4 K, where we measure a dark count rate below 1 s-1 and a detection efficiency of 2.5(3)%. We further discuss the design of our cryogenic fluorescence-detection trap and analyze the performance of our detection system by fluorescence spectroscopy of 9Be+ ion clouds during several runs of our sympathetic laser-cooling experiment.

BASE-STEP: A transportable antiproton reservoir for fundamental interaction studies.

Currently, the world's only source of low-energy antiprotons is the AD/ELENA facility located at CERN. To date, all precision measurements on single antiprotons have been conducted at this facility and provide stringent tests of fundamental interactions and their symmetries. However, magnetic field fluctuations from the facility operation limit the precision of upcoming measurements. To overcome this limitation, we have designed the transportable antiproton trap system BASE-STEP to relocate antiprotons to laboratories with a calm magnetic environment. We anticipate that the transportable antiproton trap will facilitate enhanced tests of charge, parity, and time-reversal invariance with antiprotons and provide new experimental possibilities of using transported antiprotons and other accelerator-produced exotic ions. We present here the technical design of the transportable trap system. This includes the transportable superconducting magnet, the cryogenic inlay consisting of the trap stack and detection systems, and the differential pumping section to suppress the residual gas flow into the cryogenic trap chamber.

Ultra-thin polymer foil cryogenic window for antiproton deceleration and storage.

We present the design and characterization of a cryogenic window based on an ultra-thin aluminized biaxially oriented polyethylene terephthalate foil at T < 10 K, which can withstand a pressure difference larger than 1 bar at a leak rate <1×10-9 mbar l/s. Its thickness of ∼1.7 µm makes it transparent to various types of particles over a broad energy range. To optimize the transfer of 100 keV antiprotons through the window, we tested the degrading properties of different aluminum coated polymer foils of thicknesses between 900 and 2160 nm, concluding that 1760 nm foil decelerates antiprotons to an average energy of 5 keV. We have also explicitly studied the permeation as a function of coating thickness and temperature and have performed extensive thermal and mechanical endurance and stress tests. Our final design integrated into the experiment has an effective open surface consisting of seven holes with a diameter of 1 mm and will transmit up to 2.5% of the injected 100 keV antiproton beam delivered by the Antiproton Decelerator and Extra Low ENergy Antiproton ring facility of CERN.

BASE-high-precision comparisons of the fundamental properties of protons and antiprotons.

Abstract: The BASE collaboration at the antiproton decelerator/ELENA facility of CERN compares the fundamental properties of protons and antiprotons with ultra-high precision. Using advanced Penning trap systems, we have measured the proton and antiproton magnetic moments with fractional uncertainties of 300 parts in a trillion (p.p.t.) and 1.5 parts in a billion (p.p.b.), respectively. The combined measurements improve the resolution of the previous best test in that sector by more than a factor of 3000. Very recently, we have compared the antiproton/proton charge-to-mass ratios with a fractional precision of 16 p.p.t., which improved the previous best measurement by a factor of 4.3. These results allowed us also to perform a differential matter/antimatter clock comparison test to limits better than 3%. Our measurements enable us to set limits on 22 coefficients of CPT- and Lorentz-violating standard model extensions (SME) and to search for potentially asymmetric interactions between antimatter and dark matter. In this article, we review some of the recent achievements and outline recent progress towards a planned improved measurement of the antiproton magnetic moment with an at least tenfold improved fractional accuracy.

Enantioselective catalytic remote perfluoroalkylation of α-branched enals driven by light.

Herein, we report a photochemical organocatalytic method for the asymmetric introduction of perfluoroalkyl fragments (including the valuable trifluoromethyl moiety) at the remote γ-position of α-branched enals. The chemistry exploits the ability of extended enamines (dienamines) to form photoactive electron donor-acceptor (EDA) complexes with perfluoroalkyl iodides, which under blue light irradiation generate radicals through an electron transfer mechanism. The use of a chiral organocatalyst, derived from cis-4-hydroxy-l-proline, secures a consistently high stereocontrol while inferring complete site selectivity for the more distal γ position of the dienamines.

Photochemical Organocatalytic Functionalization of Pyridines via Pyridinyl Radicals.

We report a photochemical method for the functionalization of pyridines with radicals derived from allylic C-H bonds. Overall, two substrates undergo C-H functionalization to form a new C(sp2)-C(sp3) bond. The chemistry harnesses the unique reactivity of pyridinyl radicals, generated upon single-electron reduction of pyridinium ions, which undergo effective coupling with allylic radicals. This novel mechanism enables distinct positional selectivity for pyridine functionalization that diverges from classical Minisci chemistry. Crucial was the identification of a dithiophosphoric acid that masters three catalytic tasks, sequentially acting as a Brønsted acid for pyridine protonation, a single electron transfer (SET) reductant for pyridinium ion reduction, and a hydrogen atom abstractor for the activation of allylic C(sp3)-H bonds. The resulting pyridinyl and allylic radicals then couple with high regioselectivity.

A high-Q superconducting toroidal medium frequency detection system with a capacitively adjustable frequency range >180 kHz.

We describe a newly developed polytetrafluoroethylene/copper capacitor driven by a cryogenic piezoelectric slip-stick stage and demonstrate with the chosen layout cryogenic capacitance tuning of ≈60 pF at ≈10 pF background capacitance. Connected to a highly sensitive superconducting toroidal LC circuit, we demonstrate tuning of the resonant frequency between 345 and 685 kHz, at quality factors Q > 100 000. Connected to a cryogenic ultra low noise amplifier, a frequency tuning range between 520 and 710 kHz is reached, while quality factors Q > 86 000 are achieved. This new device can be used as a versatile image current detector in high-precision Penning-trap experiments or as an LC-circuit-based haloscope detector to search for the conversion of axion-like dark matter to radio-frequency photons. This new development increases the sensitive detection bandwidth of our axion haloscope by a factor of ≈1000.

Isothiourea-Catalyzed [2 + 2] Cycloaddition of C(1)-Ammonium Enolates and N-Alkyl Isatins.

Enantioselective [2 + 2] cycloaddition of C(1)-ammonium enolates generated catalytically using the isothiourea HyperBTM with N-alkyl isatins gives spirocyclic ß-lactones. In situ ring opening with an amine nucleophile generates isolable highly enantioenriched products in up to 92:8 dr and in >99:1 er.

A Desilylative Approach to Alkyl Substituted C(1)-Ammonium Enolates: Application in Enantioselective [2+2] Cycloadditions.

The catalytic generation of C(1)-ammonium enolates from the corresponding α-silyl-α-alkyl substituted carboxylic acids using the isothiourea HyperBTM is reported. This desilylative approach grants access to α-unsubstituted and α-alkyl substituted C(1)-ammonium enolates, which are typically difficult to access through traditional methods reliant upon deprotonation. The scope and limitations of this process is established in enantioselective [2+2]-cycloaddition processes with perfluoroalkylketones (31 examples, up to 96 % yield and >99 : 1 er), as well as selective [2+2]-cycloaddition with trifluoromethyl enones (4 examples, up to 75 % yield and >99 : 1 er). Preliminary mechanistic studies indicate this process proceeds through an initial kinetic resolution of an in situ prepared (±)-α-silyl-α-alkyl substituted anhydride, while the reaction process exhibits overall pseudo zero-order kinetics.

Lewis Base-Catalysed Enantioselective Radical Conjugate Addition for the Synthesis of Enantioenriched Pyrrolidinones.

We report a catalytic asymmetric protocol for the preparation of chiral pyrrolidinones proceeding via a radical pathway. The chemistry exploits the combination of photoredox catalysis and Lewis base catalysis to realise the first example of asymmetric radical conjugate addition to α,ß-unsaturated anhydrides and esters. The reaction is initiated by photoredox activation of N-arylglycines to generate, upon decarboxylation, α-amino radicals. These radicals are then intercepted stereoselectively by α,ß-unsaturated acyl ammonium intermediates, whose formation is mastered by a chiral isothiourea organocatalyst. Cyclisation leads to catalyst turnover and formation of enantioenriched pyrrolidinones. The utility of the protocol was demonstrated with application to the synthesis of biologically-active γ-amino butyric acids.

A 16-parts-per-trillion measurement of the antiproton-to-proton charge-mass ratio.

The standard model of particle physics is both incredibly successful and glaringly incomplete. Among the questions left open is the striking imbalance of matter and antimatter in the observable universe1, which inspires experiments to compare the fundamental properties of matter/antimatter conjugates with high precision2-5. Our experiments deal with direct investigations of the fundamental properties of protons and antiprotons, performing spectroscopy in advanced cryogenic Penning trap systems6. For instance, we previously compared the proton/antiproton magnetic moments with 1.5 parts per billion fractional precision7,8, which improved upon previous best measurements9 by a factor of greater than 3,000. Here we report on a new comparison of the proton/antiproton charge-to-mass ratios with a fractional uncertainty of 16 parts per trillion. Our result is based on the combination of four independent long-term studies, recorded in a total time span of 1.5 years. We use different measurement methods and experimental set-ups incorporating different systematic effects. The final result, [Formula: see text], is consistent with the fundamental charge-parity-time reversal invariance, and improves the precision of our previous best measurement6 by a factor of 4.3. The measurement tests the standard model at an energy scale of 1.96 × 10-27 gigaelectronvolts (confidence level 0.68), and improves ten coefficients of the standard model extension10. Our cyclotron clock study also constrains hypothetical interactions mediating violations of the clock weak equivalence principle (WEPcc) for antimatter to less than 1.8 × 10-7, and enables the first differential test of the WEPcc using antiprotons11. From this interpretation we constrain the differential WEPcc-violating coefficient to less than 0.030.

Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides.

The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of para-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er).

Evaluation of an Extended-duration Chemoprophylaxis Regimen for Venous Thromboembolism after Microsurgical Breast Reconstruction.

Patients undergoing free flap breast reconstruction are at a high risk for venous thromboembolism based upon Caprini scores. Guidelines for venous thromboembolism prophylaxis recommend high-risk groups receive extended chemoprophylaxis for several weeks after gynecological, orthopedic, and surgical oncology cases. Extended prophylaxis has not been studied in free flap breast reconstruction. The purpose of this study was to compare outcomes of free flap breast reconstruction patients who received extended venous thromboembolism (VTE) prophylaxis with those who received standard inpatient-only prophylaxis. METHODS: Patients undergoing microsurgical breast reconstruction were divided into two groups: standard VTE prophylaxis (Group I) and extended prophylaxis (Group II). Both groups received prophylactic subcutaneous heparin or enoxaparin preoperatively and enoxaparin 40 mg daily postoperatively while inpatient. Group II was discharged with a home regimen of enoxaparin 40 mg daily for an additional 14 days. RESULTS: In total, 103 patients met inclusion criteria (36 patients in Group I, 67 patients in Group II). The incidence of VTE was 1.5% in Group II compared with 2.8% in Group I (P = 0.6). There was no difference in reoperative hematoma between Group I (n = 0) and Group II (n = 1) (P = 0.7). Total flap loss was 2.2%. CONCLUSIONS: Although this retrospective pilot study did not show statistical significance in VTE between those receiving extended home chemoprophylaxis (1.5% incidence) compared with inpatient-only chemoprophylaxis (2.8%), the risk of bleeding complications was similar. These results indicate that a larger, higher powered study is justified to assess if an extended home chemoprophylaxis protocol should be standard of care post free flap breast reconstruction.

Sympathetic cooling of a trapped proton mediated by an LC circuit.

Efficient cooling of trapped charged particles is essential to many fundamental physics experiments1,2, to high-precision metrology3,4 and to quantum technology5,6. Until now, sympathetic cooling has required close-range Coulomb interactions7,8, but there has been a sustained desire to bring laser-cooling techniques to particles in macroscopically separated traps5,9,10, extending quantum control techniques to previously inaccessible particles such as highly charged ions, molecular ions and antimatter. Here we demonstrate sympathetic cooling of a single proton using laser-cooled Be+ ions in spatially separated Penning traps. The traps are connected by a superconducting LC circuit that enables energy exchange over a distance of 9 cm. We also demonstrate the cooling of a resonant mode of a macroscopic LC circuit with laser-cooled ions and sympathetic cooling of an individually trapped proton, reaching temperatures far below the environmental temperature. Notably, as this technique uses only image-current interactions, it can be easily applied to an experiment with antiprotons1, facilitating improved precision in matter-antimatter comparisons11 and dark matter searches12,13.

Maintaining Surgical Readiness While Deployed to Low-Volume Military Treatment Facilities: A Pilot Program for Clinical and Operational Sustainment Training in the Deployed Environment.

INTRODUCTION: Maintaining readiness among Army surgeons is increasingly challenging because of declining operative experience during certain deployments. Novel solutions should be considered. MATERIALS AND METHODS: A pilot program was conducted to rotate surgical teams from a military treatment facility with a low volume of combat casualty care to one with a higher volume. Pre- and postrotation surveys were conducted to measure relative operative experience, trauma experience, and perceived readiness among rotators. RESULTS: Operative volumes and trauma volumes were increased and that perceived readiness among rotators, especially those with the fewest previous deployments, was improved. CONCLUSIONS: Maintaining readiness among Army surgeons is a difficult task, but a combination of increased trauma care while in garrison, as well as increased humanitarian care during deployments, may be helpful. Additionally, rotating providers from facilities caring for few combat casualties to facilities caring for more combat casualties may also be feasible, safe, and helpful.

Preoperatively Identified Sarcopenia Leads to Increased Postoperative Complications, Hospital and ICU Length of Stay in Autologous Microsurgical Breast Reconstruction.

BACKGROUND: Sarcopenia is a condition characterized by the loss of skeletal muscle mass and strength. Recently, there has been a tremendous amount of research into the prognostic value of sarcopenia in surgical outcomes. The purpose of this study was to compare postoperative outcomes in free flap breast reconstruction in patients with and without sarcopenia. METHODS: One hundred three patients who underwent autologous breast reconstruction from 2013 to 2016 were studied. The cross-sectional area (CSA) of skeletal muscle was measured from preoperative computed tomography images at L3 using the National Institutes of Health ImageJ software. CSA was then normalized to patient stature by dividing CSA by height (cm2/m2). A previously published skeletal muscle index cutoff of 38.5 cm2/m2 was used to define sarcopenia. Intraoperative and postoperative surgical outcomes were recorded retrospectively. Outcomes were analyzed using multivariate, univariate, and regression statistics. RESULTS: Eight of the 103 (7.8%) patients were found to have sarcopenia. Sarcopenia was associated with a statistically significant increase in flap site delayed healing (37.5% vs. 20%, p = 0.046), take back to the operating room (25% vs. 11.6%, p = 0.05), intensive care unit length of stay (1.5 vs. 0.02 days, p < 0.0005), and hospital length of stay (8.38 vs. 5.49 days, p < 0.0005) when compared with patients without sarcopenia. There were no significant differences in flap loss, surgical site infection, hematoma, seroma, donor site delayed healing, intraoperative complications, and number of revision surgeries. CONCLUSION: Sarcopenia is significantly associated with increased complications in patients undergoing free flap breast reconstruction. Further investigation into the biochemical and physiologic changes associated with sarcopenia is needed.

Experimental and Computational Study of the Gas-Phase Acidities of Acidic Di- and Tripeptides.

Gas-phase acidities (GA or Δ Gacid) of acidic di- and tripeptides are determined for the first time. The peptides studied are composed of inert alanine (A) residues and one X residue of either aspartic acid (D) or glutamic acid (E): AX, XA, AAX, AXA, and XAA. Experimental GAs were measured by the thermokinetic method of deprotonation ion/molecule reactions in a Fourier transform ion cyclotron resonance mass spectrometer. Calculated GAs were obtained by composite correlated molecular orbital theory at the G3(MP2) level for deprotonation of carboxylic acid groups both at the C-terminus and at the side chain. Excellent agreement was found between experimental and calculated GA values. There is a slight preference for peptides with D being more acidic than analogous peptides with E, which agrees with the GAs of the corresponding amino acids. Experiments showed that peptides are more acidic (lower numerical GA values) when the acidic residue is located at the C-terminus (i.e., AX or AAX). The lowest energy form of deprotonated AAE has a unique structure where the longer side chain of E allows the two carboxylates, which are in close proximity, to share the proton. The tripeptides are less acidic (higher GA value) by 3-7 kcal/mol when the acidic residue is in the center. The tripeptides are more acidic (by 2-10 kcal/mol) than dipeptides containing the same acidic residue at the same location.

Revisiting the reactivity of tetrachloroauric acid with N,N-bidentate ligands: structural and spectroscopic insights.

The reactivity of tetrachloroauric acid (HAuCl4) with readily accessible bidentate N-donor ligands affords N,N-ligated Au(iii) center complexes. These compounds are useful precursors of stable catalysts, anticancer agents, and building blocks for materials. This report provides detailed insight into intermediates, equilibria, the counter anion effect, and structural variability, using spectroscopy, crystallography and computational tools. Novel mixed-valence Au(i) and Au(iii) complexes [Au(o-phen)Cl2]2[AuCl2][AuCl4] and [Au(o-phen)Cl2][AuCl2] having AuCl2- and AuCl4- anions linearly arranged in the axial sites of the square-planar Au(o-phen)Cl2 cation were discovered. Other competing side products of the reaction studied revealed protonated N,N-bidentate ligands with AuCl4- anions. Quantitative variable temperature NMR studies reveal that for a mixture of target Au(iii) salt and the protonated ligand, the reaction favors the irreversible formation of the side product. Using a rapid (30 min) temperature controlled protocol, the desired coordinated species is accessible in respectable yields while avoiding side products.

International Multicenter Validation of an Intermediate Risk Subclassification of Prostate Cancer Managed with Radical Treatment without Hormone Therapy.

PURPOSE: The NCCN Guidelines® recently endorsed a subclassification of intermediate risk prostate cancer into favorable and unfavorable subgroups. However, this subclassification was developed in a treatment heterogeneous cohort. Thus, to our knowledge the natural history of androgen deprivation treatment naïve favorable and unfavorable intermediate risk prostate cancer cases remains unknown. MATERIALS AND METHODS: Groups at 3 academic centers pooled data on patients with intermediate risk prostate cancer treated with radical monotherapy (dose escalated external beam radiotherapy, brachytherapy or radical prostatectomy) without combined androgen deprivation treatment. We used the cumulative incidence with competing risk analysis to estimate biochemical recurrence, distant metastasis and prostate cancer specific mortality. RESULTS: A total of 2,550 men at intermediate risk were included in study, of whom 1,063 and 1,487 were at favorable and unfavorable risk, respectively. Of the men 1,149 underwent radical prostatectomy, 1,143 underwent dose escalated external beam radiotherapy and 258 underwent brachytherapy. Median followup after the different treatments ranged from 60.4 to 107.4 months. The 10-year cumulative incidence of distant metastasis in the favorable vs unfavorable risk groups was 0.2% (95% CI 0.2-0.2) vs 11.6% (95% CI 7.7-15.5) for radical prostatectomy (p <0.001), 2.8% (95% CI 0.8-4.8) vs 13.5% (95% CI 9.6-17.4) for dose escalated external beam radiotherapy (p <0.001) and 3.5% (95% CI 0-7.4) vs 10.2% (95% CI 4.3-16.1) for brachytherapy (p = 0.063). The 10-year rate of prostate cancer specific mortality in the favorable vs unfavorable risk groups was 0% (95% CI 0-0) vs 3.7% (95% CI 1.7-5.7) for radical prostatectomy (p = 0.016), 0.5% (95% CI 0.5-0.5) vs 5.6% (95% CI 3.6-7.6) for dose escalated external beam radiotherapy (p = 0.015) and 0% (95% CI 0-0) vs 2.5% (95% CI 0.5-4.5) for brachytherapy (p = 0.028). CONCLUSIONS: This multicenter international effort independently validates the prognostic value of the intermediate risk prostate cancer subclassification in androgen deprivation treatment naïve cases across all radical treatment modalities. It is unlikely that treatment intensification would meaningfully improve oncologic outcomes in men at favorable intermediate risk.